Using the novel tissue microarray technique, we studied immunohistochemical expression of cell cycle regulators p53, p21, pRb in 42 grade II oligodendrogliomas, 16 grade III anaplastic oligodendrogliomas, 10 primary and 4 recidive grade II oligoastrocytomas, 10 grade III oligoastrocytomas and 2 other grade II mixed gliomas. The p53 immunopositivity associated with malignant histology of the tumor (p = 0.01, Mann-Whitney test) and high pRb expression (p = 0.015). The p21 score associated strongly with histological grade (p < 0.001). The immunopositive tumors had a significantly higher rate of proliferation (p = 0.021). The p21 immunopositivity correlated positively with p53 immunopositivity: among the 33 p21 immunopositive tumors 30 (91%) were p53 immunopositive and only 3 were p53 immunonegative (p = 0.017). Patients with p21 immunonegative primary tumors had significantly better prognosis: among them 42 of the 46 (91%) survived, whereas only 18 of the 30 patients (60%) with p21 immunopositive primary tumors survived until the follow-up date (p = 0.0017). Statistical significance was reached in multivariate analysis as well (p = 0.01, exp(B) = 5.5). The pRb immunopositive tumors had higher proliferation rate than immunonegative tumors (p = 0.002). In multivariate variance analysis, comparing the effects of different regulatory proteins on cell proliferation, only the amount of pRb expression reached statistical significance (p = 0.004). In conclusion, the expression of p21 in oligodendrocytic tumors seems to be upregulated by p53 expression which rises with cell proliferation and malignancy as in attempt to halt cell cycle but seems to be overrun by other factors. The amount of p21 expression has independent prognostic significance and could be used in diagnosis to help the difficult evaluation of the malignancy potential of oligodendrogliomas and oligoastrocytomas.