The human hematopoietic progenitor cell antigen (CD34) is a cell surface protein expressed by human hematopoietic progenitor cells, vascular endothelium, and many mesenchymal tumors. Sections from six samples of normal skin and from 41 epithelial tumors of the skin were studied. Immunostaining of epithelial cells from the external root sheath below the attachment of the arrector pili muscle and above the matrix cells was noted in normal samples. Tumors derived from or differentiated toward cells of the outer sheath, especially trichilemmomas, were immunostained with QBEND/10 (anti-CD34 antibody), whereas other epithelial tumors studied were negative. CD34 could serve as a marker of outer sheath cell derivation and may well be of value in the distinction between trichilemmomas and other lesions with similar histopathological features.