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Official Description

In situ hybridization (eg, FISH), per specimen; initial single probe stain procedure

© Copyright 2026 American Medical Association. All rights reserved.

Common Language Description

In situ hybridization (FISH) is a sophisticated laboratory technique utilized to identify and localize specific nucleic acid sequences, including DNA and RNA, within fixed tissues or cells. This method provides critical temporal and spatial information regarding gene expression and genetic coding, which is essential for understanding the organization, regulation, and functional roles of genes within biological systems. The process begins with the fixation of sample cells or tissues, which preserves the target transcripts in their original locations. Following fixation, a DNA or RNA probe is introduced, which hybridizes, or binds, to the target nucleic acid sequence at an elevated temperature. After this binding occurs, any unbound excess probe is thoroughly washed away to ensure specificity. The remaining bound DNA or RNA targets are then stained using spectrally distinct fluorophore labels, allowing for visualization under fluorescent microscopy. This technique, known as FISH, can be employed to assess various genetic characteristics, such as gene presence, copy number, and location through DNA-FISH, or to analyze gene expression and the localization of RNA through RNA-FISH. Notably, FISH has the capability to utilize multiple probes simultaneously, enabling the visualization of co-locations of different targets within a single specimen. The CPT® Code 88365 specifically refers to the initial single probe stain procedure performed on a specimen, while additional single probe stains are reported using code 88364, and the use of multiple probes in the same staining procedure is captured by code 88366.

© Copyright 2026 Coding Ahead. All rights reserved.

1. Indications

The in situ hybridization (FISH) procedure is indicated for various diagnostic and research purposes, particularly in the context of genetic analysis. The following conditions may warrant the use of this technique:

  • Genetic Mutations Identification of specific genetic mutations that may be associated with various diseases, including cancers.
  • Gene Expression Analysis Assessment of gene expression levels in different tissues or cell types, providing insights into cellular functions and disease mechanisms.
  • Chromosomal Abnormalities Detection of chromosomal abnormalities, such as deletions, duplications, or translocations, which can be critical in cancer diagnostics.
  • Developmental Studies Investigation of gene localization and expression during developmental processes, aiding in understanding developmental biology.

2. Procedure

The in situ hybridization (FISH) procedure involves several critical steps to ensure accurate localization and visualization of nucleic acid targets. The following outlines the procedural steps:

  • Step 1: Sample Preparation The first step involves preparing the tissue or cell samples. This includes fixation, where the samples are treated with fixatives to preserve the cellular structure and nucleic acids in their native state. This step is crucial for maintaining the integrity of the target sequences.
  • Step 2: Probe Hybridization After fixation, the samples are incubated with a specific DNA or RNA probe that is complementary to the target nucleic acid sequence. This hybridization occurs at an elevated temperature, which facilitates the binding of the probe to the target sequence. The conditions are optimized to ensure specificity and reduce background noise.
  • Step 3: Washing Following hybridization, the samples undergo a washing process to remove any unbound or excess probes. This step is essential to enhance the specificity of the results, ensuring that only the bound probes remain attached to the target sequences.
  • Step 4: Staining The next step involves staining the remaining bound DNA or RNA targets with spectrally distinct fluorophore labels. This staining allows for the visualization of the targets under a fluorescent microscope, enabling the identification of the specific locations of the nucleic acids within the cells or tissues.
  • Step 5: Visualization Finally, the samples are examined using fluorescent microscopy. The distinct fluorophore labels emit specific wavelengths of light, allowing for the visualization of the hybridized targets. This step is critical for interpreting the results and understanding the spatial distribution of the nucleic acids within the specimen.

3. Post-Procedure

After the completion of the in situ hybridization (FISH) procedure, several post-procedure considerations are important for ensuring accurate interpretation of results. The samples should be carefully analyzed under a fluorescent microscope to assess the presence and localization of the hybridized probes. It is essential to document the findings thoroughly, including the number of positive signals, their locations, and any relevant morphological features observed. Additionally, proper storage of the samples may be required for future reference or additional analysis. The results obtained from the FISH procedure can provide valuable insights into genetic abnormalities, gene expression patterns, and other critical biological information, which can inform further diagnostic or therapeutic decisions.

Short Descr INSITU HYBRIDIZATION (FISH)
Medium Descr IN SITU HYBRIDIZATION 1ST PROBE STAIN
Long Descr In situ hybridization (eg, FISH), per specimen; initial single probe stain procedure
Status Code Active Code
Global Days XXX - Global Concept Does Not Apply
PC/TC Indicator (26, TC) 1 - Diagnostic Tests for Radiology Services
Multiple Procedures (51) 0 - No payment adjustment rules for multiple procedures apply.
Bilateral Surgery (50) 0 - 150% payment adjustment for bilateral procedures does NOT apply.
Physician Supervisions 09 - Concept does not apply.
Assistant Surgeon (80, 82) 0 - Payment restriction for assistants at surgery applies to this procedure...
Co-Surgeons (62) 0 - Co-surgeons not permitted for this procedure.
Team Surgery (66) 0 - Team surgeons not permitted for this procedure.
Diagnostic Imaging Family 99 - Concept Does Not Apply
APC Status Indicator STV-Packaged Codes
Type of Service (TOS) 5 - Diagnostic Laboratory
Berenson-Eggers TOS (BETOS) T1G - Lab tests - other (Medicare fee schedule)
MUE 4
CCS Clinical Classification 234 - Pathology

This is a primary code that can be used with these additional add-on codes.

0848T Add On Code Resequenced Code MPFS Status: Carrier Priced APC N Digitization of glass microscope slides for in situ hybridization (eg, FISH), per specimen; initial single probe stain procedure (List separately in addition to code for primary procedure)
88364 Addon Code Resequenced Code MPFS Status: Active Code APC N In situ hybridization (eg, FISH), per specimen; each additional single probe stain procedure (List separately in addition to code for primary procedure)
26 Professional component: certain procedures are a combination of a physician or other qualified health care professional component and a technical component. when the physician or other qualified health care professional component is reported separately, the service may be identified by adding modifier 26 to the usual procedure number.
59 Distinct procedural service: under certain circumstances, it may be necessary to indicate that a procedure or service was distinct or independent from other non-e/m services performed on the same day. modifier 59 is used to identify procedures/services, other than e/m services, that are not normally reported together, but are appropriate under the circumstances. documentation must support a different session, different procedure or surgery, different site or organ system, separate incision/excision, separate lesion, or separate injury (or area of injury in extensive injuries) not ordinarily encountered or performed on the same day by the same individual. however, when another already established modifier is appropriate it should be used rather than modifier 59. only if no more descriptive modifier is available, and the use of modifier 59 best explains the circumstances, should modifier 59 be used. note: modifier 59 should not be appended to an e/m service. to report a separate and distinct e/m service with a non-e/m service performed on the same date, see modifier 25.
XU Unusual non-overlapping service, the use of a service that is distinct because it does not overlap usual components of the main service
GC This service has been performed in part by a resident under the direction of a teaching physician
TC Technical component; under certain circumstances, a charge may be made for the technical component alone; under those circumstances the technical component charge is identified by adding modifier 'tc' to the usual procedure number; technical component charges are institutional charges and not billed separately by physicians; however, portable x-ray suppliers only bill for technical component and should utilize modifier tc; the charge data from portable x-ray suppliers will then be used to build customary and prevailing profiles
XE Separate encounter, a service that is distinct because it occurred during a separate encounter
X5 Diagnostic services requested by another clinician: for reporting services by a clinician who furnishes care to the patient only as requested by another clinician or subsequent and related services requested by another clinician; this modifier is reported for patient relationships that may not be adequately captured by the above alternative categories; reporting clinician service examples include but are not limited to, the radiologist's interpretation of an imaging study requested by another clinician
AQ Physician providing a service in an unlisted health professional shortage area (hpsa)
Q1 Routine clinical service provided in a clinical research study that is in an approved clinical research study
XP Separate practitioner, a service that is distinct because it was performed by a different practitioner
CR Catastrophe/disaster related
Q6 Service furnished under a fee-for-time compensation arrangement by a substitute physician or by a substitute physical therapist furnishing outpatient physical therapy services in a health professional shortage area, a medically underserved area, or a rural area
91 Repeat clinical diagnostic laboratory test: in the course of treatment of the patient, it may be necessary to repeat the same laboratory test on the same day to obtain subsequent (multiple) test results. under these circumstances, the laboratory test performed can be identified by its usual procedure number and the addition of modifier 91. note: this modifier may not be used when tests are rerun to confirm initial results; due to testing problems with specimens or equipment; or for any other reason when a normal, one-time, reportable result is all that is required. this modifier may not be used when other code(s) describe a series of test results (eg, glucose tolerance tests, evocative/suppression testing). this modifier may only be used for laboratory test(s) performed more than once on the same day on the same patient.
XS Separate structure, a service that is distinct because it was performed on a separate organ/structure
76 Repeat procedure or service by same physician or other qualified health care professional: it may be necessary to indicate that a procedure or service was repeated by the same physician or other qualified health care professional subsequent to the original procedure or service. this circumstance may be reported by adding modifier 76 to the repeated procedure or service. note: this modifier should not be appended to an e/m service.
77 Repeat procedure by another physician or other qualified health care professional: it may be necessary to indicate that a basic procedure or service was repeated by another physician or other qualified health care professional subsequent to the original procedure or service. this circumstance may be reported by adding modifier 77 to the repeated procedure or service. note: this modifier should not be appended to an e/m service.
90 Reference (outside) laboratory: when laboratory procedures are performed by a party other than the treating or reporting physician or other qualified health care professional, the procedure may be identified by adding modifier 90 to the usual procedure number.
GA Waiver of liability statement issued as required by payer policy, individual case
GV Attending physician not employed or paid under arrangement by the patient's hospice provider
GW Service not related to the hospice patient's terminal condition
GY Item or service statutorily excluded, does not meet the definition of any medicare benefit or, for non-medicare insurers, is not a contract benefit
GZ Item or service expected to be denied as not reasonable and necessary
Q0 Investigational clinical service provided in a clinical research study that is in an approved clinical research study
Date
Action
Notes
2024-01-01 Changed Guideline added.
2015-01-01 Changed Description Changed
2005-01-01 Changed Code description changed.
Pre-1990 Added Code added.
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