The histogenesis of clear cell sarcoma was investigated by immunohistochemical examination of five tumors (two melanotic and three amelanotic) and electron microscopic examination of two of these tumors (one melanotic and one amelanotic). Melanin production was observed histologically in two of the tumors. The cytoplasm of cells in both types of tumor contained various numbers of melanosomes. Melanoma-specific antibody (HMB-45), anti-S-100 protein, and anti-vimentin antibodies gave positive reactions in four tumors, while all tumors showed Leu-7 immunoreactivity. No cytokeratin or epithelial membrane antigen (EMA) was detected immunohistochemically in any tumor. The immunoreactivity of this type of tumor with HMB-45 antibody strongly suggests melanocytic differentiation rather than schwannian or synovial differentiation. The reaction of the cells of one tumor with only Leu-7 indicates the existence of undifferentiated clear cell sarcoma of neuroectodermal origin that does not show definite melanocytic differentiation.