Carcinomas that arise in a proliferating trichilemmal cyst (PTC) have been described under a variety of names. Monoclonal antibodies (mAbs) indicating follicular differentiation have become available and were used here in two rare tumors with uncommon biologic behavior. To further elucidate the histogenesis of carcinomas arising in a PTC, mAbs to hair follicle stem cells and to hair follicle differentiation-specific cytokeratins (mAbs to cytokeratin [CK] 7, CK8, CK18, and CK19 as well as mAbs to CD8/CK15 and CD34) were studied on paraffin-embedded sections of two cases of carcinoma arising in a PTC, one anaplastic carcinoma, and one poorly differentiated squamous cell carcinoma (SCC). For comparison, concurrent PTCs and trichilemmal cysts as well as four SCCs from controls were studied. The anaplastic carcinoma showed expression of CK7, indicating a fetal hair root phenotype, and expression of CD34, indicating trichilemmal differentiation. In contrast, the poorly differentiated SCCs as well as the control SCCs stained negative for most of the mAbs applied. Expression of fetal and trichilemmal hair follicle phenotypes suggests differentiation from hair stem cells and might explain differences in biologic behavior.