Summary & Overview

CPT 88373: In Situ Hybridization Single Probe with Computer-Assisted Enumeration

CPT code 88373 designates an additional in situ hybridization (ISH) single probe stain performed on slides from the same patient specimen as an initial probe stain, with results processed by computer-assisted enumeration and interpreted by a qualified provider, typically a pathologist. This code is used when a laboratory analyst applies an extra ISH probe and the slides undergo automated counting or estimation prior to professional interpretation. Nationally, CPT code 88373 matters for pathology workflows, diagnostic accuracy in tumor evaluation, and laboratory service billing for molecular diagnostic procedures. Key payers addressed in this analysis include Aetna, Blue Cross Blue Shield, Cigna Health, UnitedHealthcare, and Medicare. Readers will gain a concise understanding of the clinical context and laboratory service model for CPT code 88373, the typical sites of service where it is performed, and which major payers commonly cover or adjudicate claims for this service. The report summarizes billing and coding considerations, common modifiers used with lab and professional components, and relevant clinical implications for pathology departments and molecular laboratories. Data not available in the input for detailed payer-specific reimbursement rates, associated taxonomies, and ICD-10 pairings.

AetnaBlue Cross Blue ShieldCigna HealthUnitedHealthcareMedicare88373CPTin situ hybridizationmolecular pathologycomputer-assisted enumerationpathology laboratoryoncology diagnosticslab billing

Billing Code Overview

CPT code 88373 describes an additional in situ hybridization (ISH) single probe stain applied to slide(s) prepared from the same patient specimen as the initial probe stain, commonly performed on tumor tissue. The procedure includes slide processing with computer-assisted technology to count or estimate probe signals, followed by a pathologist or other qualified provider evaluating the stained slides, reviewing the computer enumeration, and interpreting results to provide a pathologic diagnosis.

Service type: Laboratory pathology — molecular diagnostic ISH with computer-assisted enumeration

Typical site of service: Anatomic pathology laboratory or hospital pathology department

Data not available in the input.

Clinical & Coding Specifications

Clinical Context

A 62-year-old patient with a previously biopsied breast mass undergoes tissue sampling. The specimen is submitted to the pathology laboratory where an initial in situ hybridization (ISH) single-probe stain was performed to evaluate gene copy number or target amplification. The laboratory analyst applies an additional 88373 in situ hybridization single probe stain on additional slide(s) cut from the same patient specimen when further quantitation or confirmation is required. Computer-assisted image analysis is used to enumerate probe signals or estimate probe counts. A board-certified pathologist reviews the stained slides and the computer-generated counts, integrates morphologic findings, and issues a diagnostic report (for example, assessing HER2 amplification status or other gene copy alterations) that guides oncology treatment planning. Typical workflow steps include slide preparation, ISH staining with an additional probe, digital image acquisition and automated counting, pathologist review and sign-out, and result reporting to the treating clinician. Typical site of service is the hospital-based or freestanding clinical pathology laboratory performing anatomic pathology testing.

Coding Specifications

Modifier	Description	When to Use
`26`	Professional component	Use when billing only the pathologist's interpretation component separate from technical lab work.
`TC`	Technical component	Use when billing only the laboratory technical component (staining, imaging, computer enumeration).
`59`	Distinct procedural service	Use when a distinct and separate ISH procedure on the same specimen is unrelated to another service and needs separation.
`76`	Repeat procedure by same physician	Data not available in the input.
`77`	Repeat procedure by another physician	Data not available in the input.
`90`	Reference (outside) laboratory	Use when the ISH testing is performed by an outside reference laboratory.
`80`	Assistant surgeon	Use only if a qualified assistant was appropriate in a surgical setting; rarely applicable to lab procedures.
`82`	Assistant surgeon (when qualified resident not available)	Rarely applicable; used in specific institutional contexts.
`59`	Distinct procedural service	Use to indicate a separately identifiable ISH assay on slides from the same specimen when clinical circumstances support separate reporting.
`QK`	Medical direction of two or more CRNAs/Anesthetists	Data not applicable to this lab-based procedure.

Taxonomy Code	Specialty	Notes
2085P0200X	Pathology	Anatomic and clinical pathologists who interpret ISH results and issue diagnostic reports.
207R00000X	Clinical Laboratory	Laboratory directors and clinical laboratorians overseeing ISH staining, imaging, and QA.
207L00000X	Histology	Histotechnologists and histology laboratory staff who prepare and stain slides.

Related Diagnoses

ICD-10 Code	Description	Clinical Relevance
`C50.911`	Malignant neoplasm of unspecified site of right female breast	Common indication when ISH testing (e.g., HER2) is performed to assess tumor biomarkers for targeted therapy.
`C50.912`	Malignant neoplasm of unspecified site of left female breast	As above, for left-sided breast tumors requiring molecular evaluation.
`D05.90`	Unspecified carcinoma in situ of breast	ISH may be applied for biomarker assessment in select in situ lesions when clinically indicated.
`C71.9`	Malignant neoplasm of brain, unspecified	ISH can be used on tumor tissue to evaluate gene amplifications or translocations relevant to diagnosis or therapy.
`C34.90`	Malignant neoplasm of unspecified part of unspecified bronchus or lung	Pulmonary tumor specimens may undergo ISH to assess genomic alterations for targeted treatment decisions.

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`88342`	Immunohistochemistry (IHC) or special stains, per specimen; single antibody stain	Often performed before or alongside ISH to assess protein expression (e.g., HER2 IHC) that may trigger reflex ISH testing.
`88365`	Morphometric analysis, per specimen; for laboratory procedures using computer-assisted morphometry	May describe computer-assisted quantitative analysis workflows used in conjunction with ISH enumeration.
`88374`	In situ hybridization (e.g., FISH), each probe combination or multicolor probe set	Billed when a different ISH probe set or multicolor assay is applied to the specimen as a separate test; complements `88373` when additional probe combinations are needed.
`88312`	Consultation and report on surgical pathology, second opinion	May be used when a second pathologist review or consultation is requested for complex ISH interpretation.