Sphingosine-1-phosphate receptor 1 (S1P(1)) has been shown to play an important role in the migration, proliferation, and survival of endothelial cells. S1P(1) of vascular and lymphatic endothelial cells can be detected by immunostaining of paraffin-embedded sections using a rabbit anti-S1P(1) antibody. In this study, to distinguish vascular tumors from histologic mimics using immunohistochemical means, we evaluated the expression of S1P(1) in a range of vascular tumors. S1P(1) expression was observed in eight of eight hemangiomas, four of four lymphangiomas, four of four epithelioid hemangioendotheliomas, three of three Kaposi's sarcomas, and 15 of 15 angiosarcomas with vasoformative, spindle, epithelioid, and undifferentiated features. Conventional analysis and use of a tissue microarray of soft tissue tumors revealed three of 21 liposarcomas to have weak cytoplasmic staining and one of five squamous cell carcinomas to have membranous staining in a very limited area among 115 nonvascular tumors including histological mimics of angiosarcoma such as undifferentiated carcinoma, melanoma, and epithelioid sarcoma. The sensitivity with regards to the angiosarcoma cases was equal to, or even exceeded in undifferentiated angiosarcoma, that of CD31. Based on this study, S1P(1) may be a useful adjunct to CD31 in cases where a vascular neoplasm requires a differential diagnosis.