The distribution of the neural cell adhesion molecule (N-CAM; CD56) was studied immunohistochemically in acetone-fixed frozen sections of 83 soft tissue tumors and selected normal mesenchymal tissue using Leu-19 monoclonal antibody and avidin-biotin peroxidase immunostaining. Positive N-CAM immunostaining was found in gastrointestinal and uterine cells but not in vascular smooth muscle cells. Normal skeletal muscle was negative, but atrophic muscle fibers within tumors were positive. Strong and consistent immunoreactivity was seen in nerves, pheochromocytoma, malignant schwannoma, and spindle cells, but not in epithelial-like cells of synovial sarcoma, hemangiopericytoma, benign leiomyoma, and rhabdomyosarcoma. Variable staining was seen in benign schwannoma and malignant fibrous histiocytoma. Limited, usually focal N-CAM immunoreactivity was seen in desmoid tumor, dermatofibrosarcoma, and leiomyosarcoma. Although the N-CAM is consistently seen in neural tumors, it is not cell lineage specific. Changes on malignant transformation (comparing corresponding benign and malignant lesions) do not show any consistent pattern. Rather, there is neoexpression of the N-CAM in rhabdomyosarcoma, whereas there is loss of the N-CAM in leiomyosarcoma. Immunohistochemistry of the N-CAM can be a useful adjunct for characterization of soft tissue tumors, and its possible correlation with tumor behavior has to be examined in further studies.