Despite various studies, there are serious disagreements about the cellular differentiation of papillary eccrine adenoma. In the present study, 2 specimens of papillary eccrine adenoma were analyzed by immunohistochemical techniques, using a panel of monoclonal antibodies against keratins, to elucidate its differentiation. Histopathologically, the tumor was composed of multiple tubular structures lined by two or more layers of epithelial cells. The luminal cells of the tubules were flattened or cuboidal. The former were noted in large dilated tubules. The latter were usually observed in small-to-moderate-sized tubules, and formed intraluminal papillary projections in some tubules. Immunohistochemically, there were two kinds of cuboidal cells in the luminal layers of the tubules. Most of the large dilated tubules and some of the small-to-moderate-sized tubules expressed immunophenotypes similar to those of the eccrine dermal duct. The other tubular structures, including the small tubules resembling those of syringoma, expressed immunophenotypes similar to those of the transitional portions between the dermal ducts and the secretory segments of eccrine glands. From the above comparative studies, papillary eccrine adenoma is considered to differentiate towards the dermal duct and the transitional portions between the dermal ducts and the secretory segments of eccrine glands.