Pseudomyogenic (epithelioid sarcoma-like) hemangioendothelioma is a distinctive vascular neoplasm of intermediate biological potential with a predilection for young adults and frequent multifocal presentation. Pseudomyogenic hemangioendothelioma is characterized by loose fascicles of plump spindled and epithelioid cells with abundant eosinophilic cytoplasm and coexpression of keratins and endothelial markers. Recently, a SERPINE1-FOSB fusion has been identified as a consistent genetic alteration in pseudomyogenic hemangioendothelioma. FOSB gene fusions have also been reported in a subset of epithelioid hemangiomas. The purpose of this study was to assess the potential diagnostic utility of FOSB immunohistochemistry for pseudomyogenic hemangioendothelioma compared with other endothelial neoplasms and histologic mimics. We evaluated whole-tissue sections from 274 cases including 50 pseudomyogenic hemangioendotheliomas, 84 other vascular tumors (24 epithelioid hemangiomas [including 6 cases with angiolymphoid hyperplasia with eosinophilia histology], 20 epithelioid angiosarcomas, 20 epithelioid hemangioendotheliomas [17 CAMTA1 positive, 2 TFE3 positive], 10 spindle-cell angiosarcomas, and 10 epithelioid angiomatous nodules), and 140 other histologic mimics (20 each epithelioid sarcoma, proliferative fasciitis, nodular fasciitis, cellular benign fibrous histiocytoma, spindle-cell squamous cell carcinoma, spindle-cell rhabdomyosarcoma, and leiomyosarcoma). Immunohistochemistry for FOSB was performed following pressure cooker antigen retrieval using a rabbit monoclonal antibody. Diffuse nuclear immunoreactivity for FOSB (>50% of cells) was observed in 48 of 50 (96%) pseudomyogenic hemangioendotheliomas and 13 of 24 (54%) epithelioid hemangiomas (including all angiolymphoid hyperplasia with eosinophilia type). Both FOSB-negative pseudomyogenic hemangioendothelioma cases were decalcified bone tumors. Only 7 other tumors showed diffuse FOSB expression: 2 proliferative fasciitis, 2 nodular fasciitis, 1 epithelioid angiosarcoma, 1 spindle-cell angiosarcoma, and 1 epithelioid hemangioendothelioma. Of note, the FOSB-positive epithelioid hemangioendothelioma was negative for CAMTA1 and TFE3. Focal weak FOSB staining was observed in a subset of histologic mimics and is therefore not diagnostically meaningful. In conclusion, FOSB is a highly sensitive and diagnostically useful marker for pseudomyogenic hemangioendothelioma. Immunohistochemistry for FOSB may be helpful to distinguish pseudomyogenic hemangioendothelioma from histologic mimics including epithelioid sarcoma and other vascular neoplasms. As expected, a subset of epithelioid hemangiomas expresses FOSB, including angiolymphoid hyperplasia with eosinophilia. Although occasional cases of nodular and proliferative fasciitis are positive for FOSB, distinction between these tumor types and pseudomyogenic hemangioendothelioma is usually straightforward based on morphology and other immunophenotypic findings.