Cyclooxygenase-2 (COX-2) is the inducible form of the enzyme involved in the first two steps of the prostaglandins and thromboxane synthesis. Up-regulation of COX-2 is demonstrated in tumors where it can modulate tumoral progression, metastasis, multidrug resistance and angiogenesis. Selective COX-2 inhibitors are seen with growing interest in the tumors treatment. This present study reviews the COX-2 expression in 32 primary oligodendrogliomas (24 WHO II; eight WHO III) and two glioblastomas with prominent oligodendroglial features (WHO IV). Immunohistochemical results were compared with survival in order to verify the COX-2 prognostic significance. COX-2 positivity was found in 44% tumors. Median survival of the patients with a COX-2 positive lesion was 37 months; median survival of the patients with a COX-2 negative lesion was 93 months (P =0.010). Twenty-nine percent WHO grade II tumors, 87% WHO grade III, 50% WHO grade IV resulted COX-2 positive (P =0.016). In patients affected by WHO grade II oligodendroglioma, median survival was 24 and 96 months, respectively, in COX-2 positive and negative lesions (P =0.012). In conclusion, even if further studies on different, homogeneous and larger series in vivo are certainly necessary, it is believed that COX-2 could really have a prognostic value and can be considered as a possible therapeutic opportunity.