S100 protein is a sensitive marker for melanomas and peripheral nerve sheath 
tumors. It is, however, expressed by other mesenchymal and epithelial tumors. 
Despite its low specificity, S100 protein is valuable for the diagnosis of 
desmoplastic melanomas and peripheral nerve sheath tumors, for which no specific 
marker is available. Sox10 is a neural crest transcription factor crucial for 
specification, maturation, and maintenance of Schwann cells and melanocytes. 
Anti-Sox10 antibody was applied to a variety of neural crest-derived tumors, 
mesenchymal and epithelial neoplasms, and normal tissues. Sox10 nuclear 
expression was found in 76 of 78 melanomas (97%) and 38 of 77 malignant 
peripheral nerve sheath tumors (49%) whereas S100 protein was expressed in 71 
melanomas (91%) and 23 malignant peripheral nerve sheath tumors (30%). Sox10 was 
diffusely expressed in schwannomas and neurofibromas. Sox10 reaction was seen 
only in sustentacular cells of pheochromocytomas/paragangliomas, and 
occasionally carcinoid tumors from various organs, but it was not seen in the 
tumor cells. In normal tissues, Sox10 was expressed in Schwann cells, 
melanocytes, and myoepithelial cells of salivary, bronchial, and mammary glands. 
Sox10 reaction was not identified in any other mesenchymal and epithelial tumors 
except for myoepitheliomas and diffuse astrocytomas. Sox10 was expressed by 
metastatic melanomas and nodal capsular nevus in sentinel lymph nodes, but not 
by other lymph node components such as dendritic cells. Our results indicate 
that Sox10 will serve as a more sensitive and specific marker for the diagnosis 
of melanocytic and schwannian tumors than S100 protein.