S100 proteins are low-molecular-weight, calcium-binding proteins with a broad range of functions that include regulating apoptosis, proliferation, migration, energy metabolism and inflammation. In immunohistochemistry, general S100 antibodies are used as myoepithelial cell markers, and are positive in schwann cells, neurons, glial cells, adipocytes, melanocytes, dendritic cells and chrondrocytes. They are used to identify tumors with myoepithelial cells, and are also useful for diagnosing tumors of unknown origin. They help illustrate nerve sheath involvement of tumors, and they can be used to distinguish benign nerve sheath tumors, which are strongly positive, from malignant peripheral nerve sheath tumors, which are generally negative or weak for S100. Among cancers, they are positive in melanomas, soft tissue clear cell sarcomas, histiocytic tumors, myoepithelial tumors and glial tumors. In immunohistochemistry, S100 antibodies have cytoplasmic and nuclear positivity. References: Am J Surg Pathol 2005;29:1042, PMID: 16006798; Front. Immunol. 8:1908. doi: 10.3389/fimmu.2017.01908; Curr Mol Med. 2013 Jan;13(1):24-57, PMID: 22834835