The molecular genetic events involved in the development of ependymal neoplasms are not well understood. This study retrospectively examines 41 ependymomas; in all tumors the cyclin D1 labeling index (LI) (percent of positive immunostaining tumor cells) was correlated with MIB-1 LI and outcome. The study included 41 patients (25 males and 16 females) ranging in age from 1.5 to 70 years (mean, 30.7 years). Twenty-five patients underwent a subtotal resection or biopsy, and 16 underwent a gross total resection. Thirty-two patents had an ordinary or tanycytic ependymoma, and 9 had anaplastic/malignant tumors. The cyclin D1 LI ranged from 0 to 8.2 (mean, 0.7); 21 tumors had an LI of 0, and 8 had an LI of >1.0. The MIB-1 LI ranged from 0.1 to 34 (mean, 4.6); 16 tumors had an LI >2.0. All 8 patients with a cyclin D1 LI of>1.0 had an MIB-1 LI of >2.0. The tumors in the 6 of 8 patients with a cyclin D1 LI of > 1.0 were classified as anaplastic/malignant tumors. The findings at the most recent follow-up were as follows: alive with no evidence of tumor (n - 11; mean, 64.1 months); died with evidence of tumor (n = 11; mean, 45.9 months); alive with tumor (n = 10; mean, 39.0 months). Two patients were alive with evidence of residual disease at follow-up intervals of 7 and 16 months but were lost to further follow-up. The remaining 6 patients either were lost to follow-up or else died in the immediate postoperative period. Cyclin D1 and MIB-I LI did not reliably correlate with clinical outcome or recurrence. All tumors with an elevated cyclin D1 LI also had an elevated MIB-1 LI; however, the converse was not true. An elevated cyclin D1 LI (>1.0 in this study) appeared to be associated with anaplastic/malignant histology; however, cyclin D1 LI along with MIB-1 LI and histology did not always reliably correlate with clinical outcome.