Histopathologic grading of ependymomas is considered unreliable in terms of outcome prediction. Quantification of tumor cell proliferation may be useful for outcome prediction. We analyzed prognostic and predictive values of tumor cell proliferation rates using anti-Ki-67 antigen (MIB-1 antibody) and anti-topoisomerase-IIalpha (Topo-IIalpha) immunolabeling on tumor samples of 103 consecutive ependymoma patients 0.1 to 74.4 years of age. In this patient cohort, the following clinical and histopathologic parameters showed significant correlation with overall survival on univariate analysis: extent of resection, use of an operating microscope, radiologic imaging with computed tomography and/or magnetic resonance imaging, radiotherapy, tumor size (cutoff 3 cm), WHO grade, presence of tumor necrosis, increased cellularity, microvascular proliferation, and low/high Ki-67 and Topo-IIalpha indices (cutoff 20.5% and 9.4%, respectively). On multivariate analysis, incomplete resection and high Ki-67 index remained independent factors of adverse patient outcome. In Kaplan-Meier survival analysis, low (<20.5%) or high (> or = 20.5%) Ki-67 indices predicted favorable (> or = 5 years) or unfavorable (<5 years) patient outcome at 79% and 70%, respectively. We conclude that Ki-67 immunolabeling index is an independent prognostic factor and accurate predictor of outcome in patients with intracranial ependymoma. Thus, assessment of Ki-67 index in intracranial ependymoma is useful for outcome prediction in the routine diagnostic setting.