A case of multifocal epithelioid angiosarcoma of the femur, tibia, fibula, and astragalus in a 54-year-old man is reported. The tumor was composed of nests and cords of malignant cells with epithelioid morphology, with foci of vascular differentiation, necrosis, and hemorrhage. By immunohistochemistry, the neoplastic cells showed positivity for endothelial cell markers (CD31, CD34, factor VIII-related antigen, and Ulex europaeus agglutinin I), epithelial markers (cytokeratins and epithelial membrane antigen), and vimentin. The authors' findings point out the need for a panel of antibodies for the careful search of histologic features of vascular differentiation to correctly diagnose vascular bone tumors with epithelioid features, especially in evaluating small core biopsy specimens in which a sheetlike rather than obviously vasoformative architecture may lead to an erroneous diagnosis of metastatic carcinoma.