S100 recognizes proteins of 21-24 kDa, identified as the A and B subunits of S100 protein. S100 belongs to the family of calcium binding proteins such as calmodulin and troponin C. S100A is composed of an alpha and beta chain whereas S100B is composed of two beta chains. S100 protein is expressed in Schwannomas, ependymomas, astrogliomas, and nearly all melanomas (benign and malignant) and their metastases (1-6). Studies have also shown S100 protein is expressed in Langerhans cell tumors and interdigitating dendritic cell tumor/sarcoma (IDCT) (7). Langerhans Cell Histiocytosis (also known as histiocytosis X, eosinophilic granuloma, or Langerhans cell granulomatosis) can also be confirmed by S100 staining (8).