Melanoma-specific antibody (HMB-45) is highly specific for junctional nevi, malignant melanomas, and related lesions. Rarely have other benign or neoplastic tissues demonstrated positivity with the monoclonal antibody following purification. In the present study, four of 12 pheochromocytomas contained chief cells that reacted with HMB-45. We discuss the clinical and pathologic implications of this finding.