A total of 14 cases of clear cell carcinoma of salivary glands were evaluated by immunohistochemical methods using monoclonal antibodies to cytokeratin (K1.1 and K8.12), vimentin, S-100 alpha and beta subunits, neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), MAM-3 and MAM-6 antigens and proliferating cell nuclear antigen (PCNA), as well as polyclonal antibodies to lysozyme (Ly), lactoferrin (la) and Alpha-1-antichymotrypsin (alpha 1-Ach). Histopathologically, the carcinoma was characterized by round or polygonal tumor cells with cytoplasm that does not stain with hematoxylin and eosin, nuclei with little pleomorphism and few or no mitotic figures, and growing in solid sheets, small nests or cords with collagenous stroma. Cytokeratin KL1 and K8.12 was present in few tumor cells with almost negligible to strong reaction in all cases, vimentin in 6, GFAP in 5 cases with multiple-expression of cytokeratin K8.12, vimentin and GFAP in 5 cases. S-100 protein immunoreactivity was the most prominent feature with more intense reaction of S-100 beta than S-100 alpha subunit. NSE reactivity was seen in 6 cases. Ly, La, a1-ch, MAM-3 and MAM-6 antigens were localized in clear cells with various reaction intensities. The authors conclude that the clear tumor cells in clear cell carcinoma of salivary glands are not myoepithelial in origin but epithelial or neuroectodermal/neural crest in origin, showing ductal differentiation at the immunohistochemical level.