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The aim of this investigation was recognition of the epithelial differentiation and proliferative activity of ependymomas in the spinal cord compared with astrocytomas in the spinal cord and ependymoma in the brain. We investigated histopathological and immunohistochemical examination in thirty-five cases, including eleven ependymomas, thirteen astrocytomas in the spinal region and eleven ependymomas in the intracranial region. An anti-epithelial membrane antigen antibody (EMA), and two types of anti-cytokeratin antibodies, CAM 5.2 (45 and 52 kDa) and keratin (56 and 64 kDa) were applied as epithelial markers. The proliferative potential of the tumors was investigated using the Ki-67 labeling index (LI, %). Histologically, perivascular pseudorosettes were seen in all of the spinal and intracranial ependymomas. There were few ependymal structures in the spinal ependymomas except in the myxopapillary type. Immunohistochemical study demonstrated that nine (82%) were immunoreactive for EMA, eight (73%) were immunoreactive for CAM 5.2 and three (27%) were immunoreactive for keratin in the spinal ependymomas. In the spinal astrocytomas, no tumors were immunoreactive for EMA or CAM 5.2. One of thirteen cases was immunoreactive for keratin. The Ki-67 LI of the spinal ependymomas was lower than that of the intracranial ependymoma (p < 0.01). Epithelial differentiation was found in the ependymomas, which may reflect the differences in histological and biological features between ependymomas and astrocytomas in the spinal cord. Regional differences in ependymomas may influence not only clinical features but also histo-pathological characteristics.