Expression of CD30(Ki-1) antigen has long been considered to be restricted to activated lymphocytes and related tumors. However, expression of this antigen has also been detected in embryonal carcinomas, in nonembryonal carcinomas, in malignant melanomas, and even in some myeloid cell lines and macrophages at late stages of differentiation. In this study, using monoclonal antibody Ki-1, expression of CD30 antigen was immunohistochemically examined in frozen sections of 28 benign and 63 malignant mesenchymal tumors. The authors found CD30 expressed in two of four leiomyomas, seven of 11 leiomysarcomas, one of six rhabdomyosarcomas, two of two aggressive fibromatoses, one of three fibrosarcomas, two of four synovial sarcomas, one giant cell tumors of tendon sheaths, all five malignant fibrous histiocytomas, all three osteosarcomas, one of three Ewing's sarcomas, in a tumor cell subpopulation of two of ten malignant schwannomas, and in the Schwann cell compartment of one of two ganglioneuromas tested. Furthermore, CD30 was consistently expressed in the myoepithelial compartment of 13 fibroadenomas. However, all five lipomas, all seven liposarcomas, all three neuroblastomas, both ganglioneuroblastomas, both chondrosarcomas, and tumors of disputed origin tested were consistently CD30 negative. These findings indicate that, outside the lymphatic system, CD30 antigen is not restricted to epithelial neoplasms but may also be present in tumors of mesenchymal origin. The authors conclude that CD30 antigen, although having limited utility in the differential diagnosis of tumors of questionable histogenesis, may eventually define relevant subgroups within the main tumor categories.