ABSTRACT:The distribution of S100 protein in normal skin and various tumors involving skin was assessed using rabbit antibody to S100 protein in an immunoperoxidase reaction. In normal skin, S100 was detected in the epidermis (melanocytes and Langerhans' cells), dermis (Schwann cells, Pacinian and Meissner's corpuscles, and interdigitating reticulum cells), cells of the sweat gland apparatus, and in chondrocytes. In tumors involving skin, S100 protein was present in nevi, malignant melanomas, histiocytosis X, mixed sweat gland tumors, neural tumors, chondromas, and chondrosarcomas. Detection of S100 protein by immunostaining was useful in understanding the histogenesis of various skin tumors and in assessing the diagnosis and prognosis of a variety of skin lesions encountered in surgical pathology.