CD10 is now commonly used to differentiate atypical fibroxanthoma (AFX) from melanoma, spindle cell and dedifferentiated variants of squamous cell carcinoma and leiomyosarcoma. However, we have encountered CD10-positive tumors that mimicked AFX but proved to be myxofibrosarcomas. The purpose of this study was to evaluate CD10 expression in a wide range of mesenchymal neoplasms that may involve the skin using tissue microarrays. Our results indicate that in addition to AFX, CD10 expression is common in myxofibrosarcomas, undifferentiated pleomorphic sarcomas, dermatofibromas and dermatofibrosarcoma protuberans. Myxofibrosarcomas commonly present in the skin and may be difficult to distinguish from AFX on small biopsies and CD10 positivity may confound the diagnostic difficulty.