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Immature teratoma of the ovary is an uncommon tumor comprising 1% of ovarian malignancies. The amount of immature neuroepithelium in the teratoma is an important prognostic factor. Although the current grading system based on this criterion is widely accepted, the biological significance of immature neuroepithelium is poorly understood. In this study, we used immunohistochemistry to evaluate the expression of Oct4 (also known as Oct3 or POU5F1), a transcription factor expressed in primordial germ cells and embryonic stem cells, along with that of PAX6, a transcription factor contributing to neurogenesis, and CD56, a known marker for tumors of neural origin, in 18 cases of pure immature teratoma of the ovary. Oct4 was expressed in the immature neuroepithelium of all 7 grade-3 cases and 2 grade-2 cases. It was not expressed in 4 grade-2 cases and all 5 grade-1 cases. These tumor cells lacked CD30 or α-fetoprotein expression, which supported the diagnosis of pure immature teratoma. PAX6 was expressed in the immature neuroepithelium of all immature teratomas, but not in Oct4-positive cells. CD56 was expressed in neural components of various maturities including PAX6-positive immature neuroepithelium, but not in Oct4-positive cells. These data suggest that the expression of these markers probably reflects the differentiation status of neural tissue in immature teratomas. The finding that Oct4 expression was exclusively detected in immature neuroepithelium of high-grade immature teratomas indicates that Oct4 might serve as a promising biomarker for the diagnosis of highly malignant cases of immature teratoma.