Sox2 is a transcription factor that plays a critical role in the maintenance of the self-renewal capability of neural stem cells. This study was undertaken to investigate the expression pattern of Sox2 in mature and immature teratomas of the central nervous system. Sox2 immunohistochemistry was performed in 14 cases of central nervous system teratoma: five mature, five immature teratomas, and four mixed germ cell tumors with a prominent teratoma component. Fetal brain tissue was used as a normal control. Immunofluorescence with double labeling of stem cells and neuroglial cell markers was used for phenotyping of Sox2-positive cells. In all cases of immature teratomas, positive reactivity to Sox2 was observed in primitive neuroepithelial tissues. Sox2 was not expressed in mature tissues, except in some cuboidal or columnar epithelium of endodermal origin. In mature teratomas, Sox2 expression was limited to some endodermal epithelium in two cases, and no Sox2 expression was observed in the other three cases. The majority of Sox2-positive neuroepithelial cells also expressed neural stem cell markers, nestin and vimentin. Sox2 and neuronal and oligodendroglial markers were expressed in a mutually exclusive manner. However, mature astroglial cells coexpressed Sox2 and GFAP. In fetal brain, Sox2 was mainly expressed in ventricular and subventricular zones. Since Sox2 is strongly expressed in the primitive neuroepithelial tissues of central nervous system immature teratomas, it may be a useful biomarker for the diagnosis and quantitative grading of central nervous system immature teratomas.