Inactivation of SWI/SNF (switch/sucrose non-fermentable) chromatin remodeling complex subunits is a feature shared by select carcinomas and sarcomas with epithelioid morphology and variable keratin expression, making the distinction between carcinoma and sarcoma challenging in some cases. The tight junction-associated protein claudin-4 is a marker of epithelial differentiation that is expressed in nearly all carcinomas. Claudin-4 expression has been reported in the glandular component of biphasic synovial sarcoma but has not been systematically evaluated in other sarcoma types. In this study we assessed claudin-4 expression in SWI/SNF complex-deficient neoplasms showing loss of SMARCB1 (INI1), SMARCA4 (BRG1), or ARID1A and other sarcomas with epithelioid morphology. Immunohistochemistry for claudin-4 was performed on 130 neoplasms, including 90 soft tissue tumors with epithelioid morphology and/or SMARCB1 deficiency (20 epithelioid sarcomas (10 conventional, 10 proximal-type); 10 epithelioid angiosarcomas; 10 epithelioid hemangioendotheliomas; 15 epithelioid malignant peripheral nerve sheath tumors; 10 malignant rhabdoid tumors; 15 myoepithelial carcinomas; 10 biphasic synovial sarcomas), 10 ovarian clear cell carcinomas, 10 ovarian small cell carcinomas of hypercalcemic type, and 20 SWI/SNF complex-deficient undifferentiated carcinomas (14 SMARCB1 deficient and 6 SMARCA4 deficient, including rhabdoid carcinomas of various sites and sinonasal carcinomas). Membranous expression of claudin-4 (≥5% of cells) was observed in all biphasic synovial sarcomas (epithelial component only), all ovarian clear cell carcinomas, and 16 (80%) SWI/SNF complex-deficient undifferentiated carcinomas. All other soft tissue tumors were negative for claudin-4, with the exception of two myoepithelial carcinomas and one malignant rhabdoid tumor. Interestingly, none of the ovarian small cell carcinomas of hypercalcemic type expressed claudin-4. In summary, expression of claudin-4 is highly specific for true epithelial differentiation and may be useful to distinguish SWI/SNF complex-deficient undifferentiated carcinomas from sarcomas with epithelioid morphology. The lack of claudin-4 expression in ovarian small cell carcinomas of hypercalcemic type suggests that these tumors may be better regarded as sarcomas rather than carcinomas.