Sox2 is a key transcription factor that maintains the proliferation of neuroglial stem cells and inhibits neuronal fate commitment. Moreover, it was recently found that brain tumors contain stem cells that resemble normal neuroglial stem cells in many respects. This study was undertaken to describe Sox2 expression in various brain tumors, and to determine whether Sox2 expression is a universal feature of brain tumors, or whether its expression is limited to a specific lineage of brain tumors. Sox2 immunohistochemistry was performed on 194 brain tumor tissues of various kinds. Fetal and adult normal brain tissues obtained by autopsy and brain tissues of epilepsy patients with cortical dysplasia were used as controls. Semiquantitative reverse transcription polymerase chain reaction was used to confirm the immunohistochemical results. Double immunofluorescence was performed to characterize the lineage of Sox2-positive cells. Sox2 was found to be expressed in various glial tumors, including those with astroglial, oligodendroglial, and ependymal lineages, and in the glial components of mixed neuroglial tumors, regardless of pathologic grade. In brain tumors of embryonal origin, supratentorial primitive neuroectodermal tumors showed robust Sox2 expression, whereas medulloblastomas and pineoblastomas did not. The majority of Sox2-positive tumor cells coexpressed glial fibrillary acidic protein, and most Sox2-negative cells in medulloblastomas and pineoblastomas showed neuronal differentiation. This study suggest that Sox2 may be a tumor marker of glial lineages rather than a universal brain tumor stem cell marker, because its expression pattern was found to correspond to differentiation pathways. On the other hand, the aberrant coexpressions of Sox2 and of a neuronal marker were widely observed in glioblastomas, which reflects a disorganized differentiation pattern that characterizes highly malignant tumors.