The OCT4 transcription factor is a marker of pluripotency and is present in embryonic stem cells, primordial germ cells, and several neoplasms including seminoma, dysgerminoma, and embryonal carcinoma. Recently, immunohistochemical expression of OCT4 protein has been described in the cells within the basal layer of normal human and canine epidermis. We have examined a series of basal cell carcinomas and adnexal tumors of related histiogenesis, in an effort to corroborate the above findings and to assess for expression of OCT4 protein in neoplasia of the infundibulo-apocrine-sebaceous unit. We analyzed OCT4 expression in 115 cutaneous specimens including 26 basal cell carcinomas, 12 benign follicular tumors (10 trichoepitheliomas and 2 trichoblastomas), 10 benign apocrine tumors, 12 sebaceous hyperplasia lesions, 10 sebaceous adenomas, 4 sebaceous carcinomas, 13 nevi sebacei of Jadassohn, 8 squamous cell carcinomas (including one spindle-cell squamous cell carcinoma), 8 compound melanocytic nevi, 5 Me¨rkel cell carcinomas, 3 pilar cysts, 1 scar, 2 nonspecific, mild superficial perivascular dermatitis specimens, and 1 nonscaring alopecia. All 115 specimens examined were negative for OCT4 expression as was adjacent or overlying epidermis and follicular epithelium including the bulge region. In contrast to previous studies, our data indicate that the OCT4 expression is not retained in cutaneous neoplasms derived from basal epidermis or related adnexal neoplasms, including lesions of the scalp.