Distribution of intracytoplasmic lysozyme in proliferative and neoplastic fibrohistiocytic lesions and non fibrohistiocytic tumors was studied by immunoperoxidase technique on formalin fixed, paraffin-embedded sections. The cases examined were 161 fibrohistiocytic lesions and 86 non-fibrohistiocytic tumors. Contrary to our expectation, the lysozyme positive cells were found only in the minority of cases with fibrohistiocytic lesions. Cells positive for lysozyme were found only in 13 out of 100 cases of dermatofibroma, one out of 4 cases of xanthogranuloma and 8 out of 33 cases of malignant fibrous histiocytoma. Dermatofibrosarcoma protuberans and non-fibrohistiocytic tumors were negative for lysozyme. It is suggested that in proliferative fibrohistiocytic lesions, induction of lysozyme synthesis is weak or absent. Some malignant fibrous histiocytomas showed scattered lysozyme positive neoplastic cells, indicating their probable histiocytic origin or differentiation. On the other hand, evidence of histiocytic differentiation of dermatofibrosarcoma protuberans was not obtained using lysozyme immunohistiochemistry.