CD31 is a specific and sensitive marker of endothelial differentiation. Previous reports have described its immunoreactivity in large series of soft tissue neoplasms, as well as its comparison with other available and commonly used endothelial markers. CD31 reactivity in carcinomas or mesotheliomas has been incompletely addressed, however. Hence, we applied anti-CD31 (JC70/A, DAKO, Carpinteria, Calif) to 290 previously characterized neoplasms by using a modified avidin-biotin-peroxidase complex technique following microwave epitope retrieval. Seven carcinomas showed plasmalemmal-based immunoreactivity (2 papillary thyroid carcinomas, 2 mucoepidermoid salivary gland carcinomas, 1 cutaneous adnexal tumor, 1 cutaneous squamous cell carcinoma, and 1 esophageal squamous cell carcinoma); the remaining 283 lesions were negative for this marker. We conclude that anti-CD31 immunostaining in carcinomas and mesotheliomas is rare. These findings support the concept that CD31 is a reliable marker of endothelial differentiation and should be included in diagnostic immunohistochemical panels when vascular tumors enter the differential diagnosis.