Despite light and electron microscopic and histochemical studies, there is no consensus on the cellular differentiation of eccrine spiradenoma. In the present study, eight specimens of eccrine spiradenoma were analysed by immunohistochemical techniques, using a panel of monoclonal antibodies against cytokeratins. Two types of epithelial cells were identified in tumour nodules: large, pale epithelial cells in the centre, and small, dark epithelial cells situated at the periphery. These nodules frequently contained tubular structures lined by cuboidal, columnar or, less commonly, flattened epithelial cells. Cytokeratin expression in eccrine spiradenoma was compared with expression in normal eccrine glands. Immunohistochemistry revealed that large, pale epithelial cells expressed immunophenotypes similar to those of luminal cells in the transitional portions between the secretory portions and the coiled ducts. The small, dark cells expressed immunophenotypes similar to those of basal cells in the transitional portions. Tubular structures observed in eccrine spiradenoma showed staining patterns similar to those of the luminal cells in the transitional portions. Eccrine spiradenoma may, therefore, differentiate towards the transitional portions between the secretory portions and coiled ducts of eccrine glands. Some of the large, pale epithelial cells in eccrine spiradenoma differentiate towards tubular structures, forming a lumen lined by a cuticle.