To investigate the histogenesis of mixed tumor of the skin, apocrine type, the immunophenotypes of 10 cases were examined using 19 different monoclonal anti-keratin antibodies and antibodies against carcinoembryonic antigen (CEA) and involucrin. By using light microscopy, four epithelial elements in this tumor were characterized: tubular branching structures with lumina lined by cuboidal epithelium and those with lumina lined by columnar epithelium, keratinous cysts, and solid aggregates of epithelial cells. The immunohistochemical patterns of cytokeratin expression suggested that cuboidal and columnar cells differentiated, respectively, toward the ductal and secretory cells of apocrine glands, whereas keratinous cysts revealed follicular infundibular differentiation. Furthermore, CEA expression, a marker for sweat-gland differentiation, was present not only on tubules' luminal surfaces but also on the inner surfaces of keratinous cysts. The simultaneous coexpression of CEA and cytokeratins specific for follicular infundibulum in the keratinous cysts, although perplexing, suggested that keratinous cysts may contain some cells differentiating toward the intrafollicular portion of apocrine ducts that enter infundibulae rather than eccrine ducts that have no infundibular association. We conclude that apocrine type of mixed tumors of the skin demonstrate differentiation toward all components of apocrine units.