We carried out an immunohistochemical analysis of nine spiradenomas and seven cylindromas. Our findings underscore the histomorphological similarities of the two adnexal neoplasms-namely, the expression of S-100 protein ascribed to eccrine differentiation within the tubular and large, pale-staining cells of both entities. Human milk fat globulin (HMFG) and lysozyme, two markers associated with apocrine differentiation, are expressed by tubular cells in spiradenomas and cylindromas. Lysozyme is also expressed in cylindromas by large, pale-staining cells. In addition, antibodies to alpha-smooth muscle actin strongly characterized the small basaloid cells of both types of neoplasm. Both spiradenomas and cylindromas expressed identical cytokeratin patterns. As with the various regions of eccrine and apocrine units, the expression by spiradenomas and cylindromas of keratins 7, 8, and 18 indicates differentiation toward the secretory tissue, whereas the expression of keratin 14 in some of the neoplastic cells points toward ductal differentiation. Malformed ductal and glandular structures in continuity with evolving spiradenomas and cylindromas in two of our cases also suggest that these tumors might arise from abortive adenxal anlagen.