Epithelioid sarcoma (ES) and epithelioid hemangioendothelioma (EH) both occur preferentially in the soft tissues, and may be confused with one another microscopically. We compared 8 examples of each tumor immunohistochemically, using formalin-fixed tissue, the ABC method, unconjugated Ulex europaeus I agglutinin (UEA), rabbit antibody to UEA, and monoclonal antibodies to epithelial membrane antigen (EMA), cytokeratin (CK), factor VIII-related antigen (FVIIIRAG), and blood group isoantigens A, B, and H (BGI). Six of 8 cases of ES, and 7 of 8 epithelioid hemangioendotheliomas bound UEA; similarly, 6 of 8 ES cases were reactive for BGI, as were 4 of 8 examples of EH. All epithelioid sarcomas were positive for CK, and 7 displayed EMA, whereas these antigens were lacking in EH. Conversely, 5 of 8 cases of EH contained FVIIIRAG, which was absent in all examples of ES. These findings underscore the nonspecificity of UEA-binding and BGI-expression as markers of endothelial differentiation. Moreover, they suggest that sole reliance upon these immunohistologic reactants for the identification of vascular tumors may result in diagnostic error. Inasmuch as ES and EH differ in biological behavior, such a mistake would be significant. Thus, we advocate the inclusion of immunostains for EMA, CK, and FVIIIRAG in the evaluation of histologically-similar cases of epithelioid sarcoma and epithelioid hemangioendothelioma.