The presence of S-100 protein was immunohistochemically studied in many types of formalin-fixed and paraffin-embedded tumors (260 cases). Peripheral nerve tumors, i.e., schwannomas, neurofibromas, granular cell tumors, and neurogenic sarcomas were demonstrated to contain variable amounts of S-100 protein in the tumor cell cytoplasm and nuclei. In ganglioneuromas and ganglioneuroblastomas, neoplastic Schwann cells or satellite cells were positive for S-100 protein. About one-half of the cases of carcinoid tumors stained weakly for S-100 protein. In addition to these nervous tissue and carcinoid tumors, chondrosarcoma, chordomas, pleomorphic adenomas of the salivary gland, and Langerhans cell granulomatosis were also shown to produce S-100 protein. In many types of breast tumors and other lesions, S-100 protein positive cells were likely to correspond to the distribution of myoepithelial cells. These results indicate that S-100 protein is not strictly specific to nervous tissue and its tumors; however, the immunohistochemical demonstration of S-100 protein can be a useful diagnostic tool in tumor diagnosis.