Merkel cells are normal constituents of the basal layer of the epidermis and the follicular epithelium. They have been identified in benign neoplasms with follicular germinative differentiation but seem to be absent in basal cell carcinomas (BCCs). Because sclerosing epithelial neoplasms are often sampled by small biopsies, any method that enables distinction among them would be welcome. We used immunohistochemical staining for cytokeratin 20 to assess the presence of Merkel cells in 14 cases of desmoplastic trichoepithelioma (DTE), 12 specimens of syringoma, 11 samples of morpheiform BCC, and 8 specimens of microcystic adnexal carcinoma (MAC). Merkel cells were found in association with all 14 specimens of DTE and in 1 of 11 cases of morpheiform BCC (p < 0.005) but in none of the specimens of syringoma or MAC. Our study supports previous findings that Merkel cells are seen in association with cutaneous neoplasms that are benign and of a follicular germinative origin. Although MAC may differentiate along follicular-sebaceous-apocrine lines, the absence of Merkel cells within it is consistent with its malignancy. The identification of Merkel cells in a sclerosing epithelial neoplasm of the skin points to DTE as the most likely diagnosis.