The histopathology of 66 children with the diagnosis of ependymoma who were operated on at our institution between 1954 and 1994 were reviewed. We performed an initial analysis using the entire study cohort to determine which histopathological features associated with each other in a statistically significant fashion in an attempt to identify combinations of features that together might be useful in predicting outcome. A detailed outcome analysis was then performed on the 37 most recent cases who survived the postoperative period, in whom pre- and post-imaging studies as well as long term follow-up were obtained, in order to identify the histopathological features and combinations of features that were predictive of overall and progression-free survival. Five- and ten-year progression-free survivals were 45.1% and 36.1%, respectively. Overall survivals were 57.1% and 45.0%, respectively. Of the eight individual histopathological features, only the presence of necrosis was found to correlate with a less favorable overall and progression-free survival (PFS) (p = 0.06 and 0.03, respectively). In addition, the combination of necrosis with vascular proliferation or nuclear pleomorphism was associated with a worse PFS (p = 0.01 and 0.02, respectively). However, when other clinical predictive factors were included in a multivariate regression analysis, none of the histological features or combinations of features were independently associated with outcome. In addition, no relationship was found between the pattern of rosettes (true rosette, pseudorosette, or perivascular pseudorosette) and clinical outcome. In conclusion, although this study found an association between certain histopathological features and clinical outcome in children with ependymomas, these relationships did not reach statistical significance on multivariate analysis and, thus, do not provide sufficient evidence for modifying therapy based on histopathology alone.