Summary & Overview

CPT 88368: In Situ Hybridization Single Probe with Pathologist Evaluation

CPT code 88368 covers in situ hybridization (single probe) testing where a lab analyst performs the initial stain on slide(s) derived from a single patient specimen and a qualified provider—typically a pathologist—evaluates the stained slides, including manual counting or estimation of probe number and location. This code is central to molecular pathology workflows for tumor and other tissue-based diagnostics and supports clinical decision-making for targeted therapies and prognostic assessment. Nationally, accurate coding of 88368 ensures appropriate recognition of the professional interpretive component of single-probe ISH testing and aligns billing with laboratory and pathology service delivery.

Key payers referenced in the analysis include Aetna, Blue Cross Blue Shield, Cigna Health, UnitedHealthcare, and Medicare. Readers will find a concise overview of the code’s clinical role, expected sites of service, and common billing considerations. The publication outlines benchmark metrics for utilization and reimbursement where available, notes relevant policy updates affecting molecular pathology reporting, and situates 88368 within related pathology service lines. Data not available in the input will be identified as such in the detailed sections. The coverage is intended for a national audience of health policy analysts, billing professionals, and clinical laboratory leaders.

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Billing Code Overview

CPT code 88368 describes an in situ hybridization (single probe) procedure in which a laboratory analyst performs the initial staining on slide(s) prepared from a single patient specimen, commonly tumor tissue. A qualified provider, typically a pathologist, subsequently evaluates the stained slide(s), which includes manual counting or estimation of probe number and location.

Service type: Laboratory pathology procedure — in situ hybridization (single probe) with professional interpretation and manual probe counting.

Typical site of service: Hospital pathology laboratory, independent pathology or molecular diagnostics laboratory, or outpatient surgical pathology lab where tumor or other tissue specimens are prepared and reviewed by a pathologist.

Clinical & Coding Specifications

Clinical Context

A 62-year-old patient presents with a biopsy-proven epithelial tumor of the lung. The surgical pathology lab receives formalin-fixed paraffin-embedded tumor tissue submitted on glass slides. A histology technologist prepares new unstained sections and the laboratory analyst applies an initial in situ hybridization single-probe stain (e.g., for ALK or HER2) to one or more slides from the single patient specimen. A board-certified pathologist reviews the stained slides microscopically, documents probe signal patterns, and performs manual counting or estimation of probe numbers and locations to determine gene amplification, translocation, or copy-number changes. The report includes interpretive comments, assay controls, and a result used by the treating oncologist to guide targeted therapy.

Coding Specifications

Modifier	Description	When to Use
`26`	Professional component	Use when billing only the pathologist's interpretive component separate from the technical staining and slide preparation.
`TC`	Technical component	Use when billing only the staining and laboratory technical processing (no professional interpretation).
`90`	Reference (outside) laboratory	Use when the test was performed by an outside independent laboratory and reported by the billing lab.
`91`	Repeat clinical diagnostic laboratory test	Use when a repeat ISH is performed on the same specimen for confirmation within a defined timeframe.
`59`	Distinct procedural service	Use when another distinct laboratory procedure or separate diagnostic test is performed on the same date that is not typically bundled.
`62`	Two surgeons — co-surgery (analogous for pathology teams)	Rarely used; applies where two qualified providers share substantive portions of the evaluation/report.
`80`	Assistant surgeon	Not commonly used for pathology CPTs but applicable when an assisting qualified provider contributes to the interpretive component.
`22`	Increased procedural services	Use when the interpretive effort or complexity of counting probes is substantially greater than typical and documented.
`52`	Reduced services	Use when the procedure is partially reduced or not completed as originally planned (e.g., limited probe evaluation).
`59`	Distinct procedural service	Use for separate, unrelated lab procedures on the same specimen/date requiring independent reporting.

Taxonomy Code	Specialty	Notes
`207RP1000X`	Anatomic Pathology	Pathologists who perform slide interpretation and reporting for ISH assays.
`207L00000X`	Molecular Genetic Pathology	Specialists performing molecular interpretation and oversight of in situ hybridization testing.
`207Q00000X`	Clinical Pathology	Laboratory directors who oversee technical components and quality control of diagnostic assays.
`208000000X`	Hematopathology/Oncologic Pathology	Pathologists with expertise in neoplastic processes commonly ordering ISH studies.

Related Diagnoses

ICD-10 Code	Description	Clinical Relevance
`C34.90`	Malignant neoplasm of bronchus and lung, unspecified, unspecified site	Lung carcinoma specimens commonly undergo ISH for actionable genetic alterations (e.g., ALK, ROS1).
`C50.912`	Malignant neoplasm of unspecified site of left female breast	Breast cancers frequently receive HER2 ISH testing to assess gene amplification for therapeutic decisions.
`C71.9`	Malignant neoplasm of brain, unspecified	Central nervous system tumors may be evaluated with ISH for diagnostically relevant genomic alterations.
`C67.9`	Malignant neoplasm of bladder, unspecified	Urothelial carcinomas may undergo ISH for copy-number changes or viral probes as part of workup.
`D09.0`	Carcinoma in situ of bronchus and lung	In situ lesions may be tested with ISH when molecular characterization is indicated for management.

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`88342`	Immunohistochemistry or immunocytochemistry, per specimen; initial single antibody stain	Often performed before or in parallel with ISH to characterize tumor phenotype and guide selection of ISH probes.
`88360`	Morphometric analysis; image analysis, per specimen	May be used when digital image analysis supplements manual counting of ISH probe signals.
`88365`	Laser capture microdissection (for molecular analysis)	Performed on tissue when enrichment of tumor cells is required prior to molecular testing complementary to ISH.
`88271`	Molecular cytogenetics; ISH, per probe, interpretation and report	Related molecular cytogenetics codes for reporting ISH when different coding conventions apply or multiple probes are evaluated.
`88368`	In situ hybridization (initial single probe stain) with pathologist evaluation	The primary procedure described; stain applied by lab analyst and evaluated by a pathologist with manual counting/estimation.