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    v1.0.28
    OpenPayerBilling CodesSurgical Pathology ProceduresCPT cpt-88374-multiplex-in-situ-hybridization-pathology-interpretation
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    CPT 88374: Multiplex In Situ Hybridization Single-Probe, Pathology

    Medicare pays $186 on average nationally for this procedure.

    CPT code 88374 describes a pathology service in which a laboratory analyst applies a single multiplex in situ hybridization probe stain to slides prepared from a single patient specimen (for example, tumor tissue), processes the slides with computer-assisted technology to count or estimate probe signals, and a qualified provider interprets the stained slides and computer enumeration to render a pathologic diagnosis; service type: laboratory molecular pathology procedure using in situ hybridization with computer-assisted enumeration; typical site of service: clinical laboratory or hospital pathology lab, processing patient surgical or biopsy tissue specimens.

    For related coverage guidance, see recent payer policy updates: Onychomycosis diagnostic testing and coverage, Topical Acne-Non-Retinoid Products, Dermatology - Vtama Drug Quantity Management Policy - Per Days.

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    Table of contents

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    Clinical & Coding Specifications

    Clinical Context

    A 62-year-old patient with a recently biopsied breast mass is undergoing molecular testing to determine HER2 gene copy number and amplification status. The surgical pathology lab receives formalin-fixed, paraffin-embedded tumor tissue sections and prepares slides. A histology technologist or laboratory analyst applies a single multiplex in situ hybridization (ISH) probe stain to the slides (88374) and runs the stained slides through computer-assisted image analysis to count or estimate probe signals. A board-certified pathologist reviews the stained slides, evaluates the computer-assisted enumeration, integrates morphologic findings, and issues a final pathology report with interpretation of gene amplification status to guide targeted therapy decisions. Typical site of service is a hospital-based or independent clinical pathology laboratory affiliated with an outpatient oncology clinic or inpatient hospital. The service type is diagnostic molecular pathology testing performed on tissue (cytogenetic/molecular ISH) with both a technical component (slide preparation, staining, image analysis) and a professional component (pathologist interpretation). Typical scenario includes pre-treatment biomarker assessment for cancer management and therapeutic selection.

    Related CPT Codes

    CPT CodeDescriptionRelationship to This Procedure
    88342Immunohistochemistry, per specimen; initial single antibody stainPerformed on tissue to detect protein expression (e.g., HER2 IHC) often done before or alongside ISH testing to triage cases for 88374.
    88374In situ hybridization (e.g., FISH), single probe stain, computer-assisted interpretationThe focal procedure: multiplex ISH with computer-assisted enumeration and pathologist interpretation.
    88381Morphometric analysis; single or multiplex in situ hybridization, manual counting (if applicable)Alternative/or additional reporting when manual counting or morphometric review is performed instead of or in addition to computer-assisted enumeration.
    88360Microdissection for molecular analysisMay be performed prior to ISH on heterogeneous tumor specimens to enrich tumor content for accurate probe assessment.
    88313Consultation and review of slides from an outside source (pathology consultation)Used when a second opinion pathology review is requested for ISH-stained slides or interpretation confirmation.

    Related Modifiers

    7 rows

    ModifierDescriptionWhen to Use
    26Modifier 26 (Professional Component) identifies and bills only the professional portion of a split service — the physician’s interpretation, report, and medical judgment — when the technical…- Use CPT Modifier -26 when you are billing only the professional component (PC) of a split‑bill eligible service—i.e., you performed the physician interpretation, medical judgment and prepared a…
    90Modifier ‑90 (Reference/Outside Laboratory) indicates that a laboratory test was performed by an entity other than the treating or reporting provider. The American Medical Association defines…- Use CPT modifier -90 when a laboratory test is performed by an outside/reference laboratory (an entity other than the treating or reporting physician or qualified professional) and the claim needs…
    91Modifier 91 — “Repeat Clinical Diagnostic Laboratory Test” — is appended when the exact same CPT laboratory test is performed more than once for the same patient on the same day because serial,…- Use modifier 91 when the exact same CPT laboratory test is performed more than once on the same patient on the same date because serial or repeated testing is medically necessary to monitor…
    59Modifier 59 indicates a distinct procedural service when two procedures that are not normally billed together are clinically and procedurally separate. The CPT definition (as reiterated by CMS)…- Use modifier -59 to report a distinct procedural service when documentation supports that the procedure reported is not normally billed together with another service on the same day because of a…
    52Modifier ‑52 (Reduced Services) indicates that a service or procedure was partially reduced or omitted at the provider’s discretion, allowing reporting of the basic procedure number with a qualifier…- Use modifier -52 when a physician or qualified health professional electively reduces or omits part of a procedure or service (for example, performing fewer required views or omitting a portion of…
    53Modifier 53 (Discontinued Procedure) signals that a surgical or diagnostic service was begun by the physician but terminated because of extenuating circumstances that threatened the patient’s…- Use modifier -53 when a physician/qualified healthcare professional has started a surgical or diagnostic procedure (e.g., anesthesia administered, incision or scope insertion) and then discontinues…
    62Modifier 62 indicates that two surgeons function as co‑surgeons, each performing distinct parts of the same primary surgical procedure. It is appended to the primary procedure code (and any…- Use modifier -62 when two surgeons act as co‑surgeons (both primary surgeons) on a single definitive primary procedure, each performing distinct parts of the same surgical procedure (append -62 to…

    Related Provider Taxonomies

    8 rows

    Taxonomy CodeSpecialtyNotes
    207K00000XAllergy & Immunology PhysicianAn allergist-immunologist is trained in evaluation, physical and laboratory diagnosis, and management of disorders involving the immune system. Select…
    207L00000XAnesthesiology PhysicianAn anesthesiologist is trained to provide pain relief and maintenance, or restoration, of a stable condition during and immediately following an opera…
    332B00000XDurable Medical Equipment & Medical SuppliesA supplier of medical equipment such as respirators, wheelchairs, home dialysis systems, or monitoring systems, that are prescribed by a physician for…
    183700000XPharmacy TechnicianA person who works under the direct supervision of a licensed pharmacist and performs many pharmacy-related functions that do not require the professi…
    176B00000XMidwifeA Midwife is a trained professional with special expertise in supporting women to maintain a healthy pregnancy birth, offering expert individualized c…
    364SH0200XHome Health Clinical Nurse SpecialistPhysician Assistants & Advanced Practice Nursing Providers · Clinical Nurse Specialist
    173000000XLegal MedicineThe specialty areas of medicine concerned with matters of, and relations with, substantive law and legal institutions; such as the conduct of medical …
    281P00000XChronic Disease Hospital(1) A hospital including a physical plant and personnel that provides multidisciplinary diagnosis and treatment for diseases that have one or more of …

    Related ICD-10-CM Codes

    25 rows

    ICD-10-CM CodeDescription
    C25.9Malignant neoplasm of pancreas, unspecified
    C34.90Malignant neoplasm of unspecified part of unspecified bronchus or lung
    C44.91Basal cell carcinoma of skin, unspecified
    C50.911Malignant neoplasm of unspecified site of right female breast
    C50.912Malignant neoplasm of unspecified site of left female breast
    C53.9Malignant neoplasm of cervix uteri, unspecified
    C56.9Malignant neoplasm of unspecified ovary
    C61Malignant neoplasm of prostate
    C71.3Malignant neoplasm of parietal lobe
    C71.9Malignant neoplasm of brain, unspecified

    Showing 1–10 of 25

    Related Payer Policy Updates

    Specialty: Dermatology1 / 3

    10 rows

    PolicyPayerEffective Date
    Onychomycosis diagnostic testing and coverageOscar Health2026-10-01
    Topical Acne-Non-Retinoid ProductsCigna2026-08-15
    Dermatology - Vtama Drug Quantity Management Policy - Per DaysCigna2026-08-15
    Medical Necessity Guidelines: Acne and Rosacea Medicationsharvard pilgrim health care2026-08-11
    Pharmacologic Treatment of PsoriasisPremera Bluecross2026-08-01
    Winlevi (clascoterone 1% cream) — Topical AcneCigna2026-08-01
    Spevigo (spesolimab‑sbzo) for generalized pustular psoriasisUnitedHealthcare2026-08-01
    Onychomycosis Testingblue cross blue shield - louisiana2026-08-01
    Spesolimab-sbzo (Spevigoblue cross blue shield - tennessee2026-07-31
    Home ultraviolet light therapy equipment for skin conditionsselect_health2026-07-01

    Related Codes

    CPT-88300-LEVEL-I-SURGICAL-PATHOLOGY-GROSS-EXAMINATION-ACCESSIONING

    CPT 88300: Surgical Pathology, Level I Gross Examination

    CPT-88302-SURGICAL-PATHOLOGY-LEVEL-II-GROSS-AND-MICROSCOPIC-EXAMINATION

    CPT 88302: Surgical Pathology, Level II Gross and Microscopic Exam

    CPT-88304-SURGICAL-PATHOLOGY-LEVEL-III-GROSS-AND-MICROSCOPIC

    CPT 88304: Surgical Pathology, Level III Examination

    CPT-88305-SURGICAL-PATHOLOGY-LEVEL-IV-EXAMINATION

    CPT 88305: Surgical Pathology, Gross and Microscopic Examination, Level IV

    CPT-88307-SURGICAL-PATHOLOGY-LEVEL-V-EXAMINATION

    CPT 88307: Surgical Pathology Level V Examination

    CPT-88309-LEVEL-VI-SURGICAL-PATHOLOGY-EXAMINATION

    CPT 88309: Level VI Surgical Pathology Examination

    CPT-88311-DECALCIFICATION-SPECIMEN-PREPARATION

    CPT 88311: Decalcification Procedure for Tissue Specimens

    CPT-88312-SPECIAL-STAIN-MICROORGANISMS-TECHNICAL-COMPONENT

    CPT 88312: Special Stain, Technical Component for Microorganisms

    CPT-88313-SPECIAL-STAIN-TECHNICAL-COMPONENT

    CPT 88313: Technical Special Stain for Group II (e.g., iron, trichrome)

    CPT-88314-FROZEN-TISSUE-HISTOCHEMICAL-SPECIAL-STAIN

    CPT 88314: Frozen Tissue Histochemical Special Stain, Interpretation

    Showing 1–10 of 47

    Frequently Asked Questions

    References

    1. 1.CPT® Codes and Descriptions. AAPC. Retrieved Aug 11, 2026.Maintains the CPT code set's official descriptions and guidelines, licensed from the American Medical Association, used as the definitional source for CPT codes on this page.
    2. 2.HCPCS Quarterly Update. Centers for Medicare & Medicaid Services (CMS). Retrieved Aug 11, 2026.CMS's quarterly release of HCPCS Level II codes and short/long descriptors, the source for HCPCS code definitions and update history.
    3. 3.ICD-10-CM Full Code List. Centers for Medicare & Medicaid Services (CMS). Retrieved Aug 11, 2026.CMS's complete ICD-10-CM diagnosis code list, used to cross-reference diagnosis codes associated with this procedure or service.
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