Continuing controversy exists concerning a possible relation between neoplastic cells of malignant fibrous histiocytoma (MFH) and the mononuclear phagocyte system. The aim of this study was to investigate the membrane and cytoenzymatic phenotype of a primary cutaneous MFH, storiform pleomorphic type, and to compare these data with ultrastructural observations. Cytoplasmic proteins (acid phosphatase, non specific esterase, alpha-1 antitrypsin, and lysozyme) suggestive of a mononuclear phagocyte origin were demonstrated in varying amounts in neoplastic cells infiltrating the dermis. Consistent with these data, two (LeuM3 and OKM5) out of four (OKM1 and LeuM1) monoclonal antibodies directed against mononuclear phagocyte antigens stained most of the neoplastic cells. Class II MCH antigens (DR and DQ) were variably expressed on distinct groups of neoplastic cells, suggesting different activation/differentiation states. The results favor the view that the present case of primary cutaneous MFH was of mononuclear phagocyte origin. However, the observed phenotypic profile was expressed on neoplastic cells irrespective of their ultrastructural morphology (histiocytic or fibroblastic). Together with previous data in the literature, the latter finding corroborates the view that distinction between these two cell types in MFH is likely to reflect divergent growth and differentiation patterns rather than histogenesis.