BACKGROUND. Trichoepithelioma (TE) and basal cell carcinoma (BCC) have many features in common both clinically and histologically. Despite these many similarities TE and BCC represent different biological entities. OBJECTIVE. Recently, bcl-2 and CD34 have been reported as reliable markers in distinguishing the two types of tumor. Transforming growth factor-beta (TGF-beta), a multifunctional regulator of both cell growth and differentiation, was evaluated in this study. METHODS. The immunohistochemical expression of TGF-beta was compared with the distribution patterns of bcl-2 and CD34 in five sees, five TEs, and seven borderline cases. RESULTS. All five TEs showed a diffuse cytoplasmic staining of tumor cells for TGF-beta, whereas four of five BCCs were TGF-beta negative. Of the seven equivocal cases of TE/BCC, five tumors demonstrated TGF-beta positivity in combination with negative bcl-2 staining corresponding to TE. The remaining two cases demonstrated the opposite staining pattern, characteristic for BCC. CONCLUSION. The TGF-beta staining pattern appears to be a helpful additional marker together with bcl-2 in differentiating between TE and BCC. The demonstrated staining differences may relate to the distinct origin and biological behavior of the two tumors and may therefore be of value in subsequent patient management. (C) 1997 by the American Society for Dermatologic Surgery, Inc.