An immunocytochemical study using a panel of commercially available antisera, has been performed to distinguish on the basis of their immunoreactivity a series of spindle cell sarcomas diagnosed solely on the histologic features: 11 malignant schwannomas (MS), 8 leiomyosarcomas (LMS) and 3 malignant fibrous histiocytomas (MFH). The results have been compared with those obtained in 12 benign and 8 malignant peripheral nerve sheath tumors (MPNST) in which the microscopic diagnosis was supported by their origin in a nerve trunk and/or in von Recklinghausen's (vR) disease. The following antisera were used: anti-S-100 protein, anti-Leu-7, anti-neuron specific enolase (NSE), anti-myelin basic protein (MBP), anti-glial fibrillary acidic protein (GFAP) and anti-actin. S-100 protein was present in 100% of benign and malignant peripheral nerve tumors and in 7/11 (63%) of MS diagnosed on histological basis only and in 3/8 (37%) LMS. MFH were negative. Leu-7 positivity was observed in 8/12 (66%) and 6/8 (75%), respectively, in benign and malignant PNS neoplasms, in 5/11 (45%) MS, 4/8 (50%) LMS and 2/3 (66%) MFH. NSE was present in 7/12 (58%) and 6/8 (75%), respectively, in benign and malignant PNS tumors, in 6/11 (54%) MS and in 1/8 (12%) LMS. MFH were negative. MBP resulted negative in peripheral nerve neoplasms and spindle cell sarcomas. GFAP positivity was observed in 2/12 (16%) and 1/8 (12%), respectively, in benign and malignant PNS neoplasms. All spindle cell sarcomas were negative. All cases of MPNST and spindle cell sarcomas showed actin immunoreactivity. These results indicate that: (1) MBP, Leu-7 and NSE do not represent markers of schwannian differentiation; (2) GFAP, although rarely expressed, may indicate schwannian differentiation, and (3) malignant peripheral nerve neoplasms and LMS share immunoreactivity for S-100, Leu-7, NSE and actin, therefore they cannot be differentiated on immunocytochemical basis using commercially available antisera.