To investigate the cellular differentiation of adenoid cystic carcinomas (ACC), a comparative immunohistochemical study of 12 normal salivary glands and eight specimens of ACC was performed. Antibodies were used against S100 protein (S), keratins (K) of various molecular weights, vimentin (V), muscle-specific actin (A), epithelial-membrane antigen, human milk fat globules, and collagen type IV. A panel of four of these antibodies (SKVA) was identified as the most helpful in characterizing cells in normal salivary glands and ACC. The immunophenotypes depended on the histologic patterns of ACC. Cells in morphologically recognizable duct structures in the cribriform and trabecular areas expressed a phenotype similar to that of the intercalated duct. Cell layers around pseudocysts and occasional cellular islands had an immunophenotype suggesting myoepithelial-cell differentiation. The most clear cut epithelial/myoepithelial bilaminar differentiation was present in areas with a trabecular pattern, in which the layers facing the stroma and the central ductal elements had SKVA phenotypes of myoepithelial and ductal differentiation, respectively. In areas with a reticular pattern, most of the cells showed ductal differentiation. Many of the cells in the cribriform and basaloid regions were immunophenotypically undifferentiated. These results indicate that ACC consists of undifferentiated cells and of cells that are differentiating toward ducts, predominantly intercalated ducts, and toward myoepithelium. These findings support previous observations by electron microscope.