OBJECTIVE: The objective of this study was to investigate the histogenesis of ectomesenchymal chondromyxoid tumors (ECTs) of the tongue. STUDY DESIGN: The biochemical characteristics of a rarely occurring tumor of the tongue were analyzed by immunohistochemistry and reverse-transcriptase polymerase chain reaction (RT-PCR), and its biological properties were assessed in primary culture in serum-free media. RESULTS: Immunohistochemistry showed that the tumor cells were strongly positive for vimentin, S-100, and glial fibrillary acidic protein (GFAP), but negative for cytokeratin and epithelial membrane antigen. In primary cultures, the cells derived from the ECT were morphologically similar to neuronal cells and expressed Nanog, GFAP, and MAP2. RT-PCR analysis of the surgical specimen was positive for OCT3/4, Sox2, Nanog, MAP2, and CD105 mRNAs. CONCLUSIONS: The results of the present study indicate that ECTs originate from the ectomesenchymal cells of the neural crest and are similar in their molecular and biological characteristics to undifferentiated mesenchymal stem cells.