Prostaglandin E2 has been connected to processes promoting tumor growth in several human malignancies including gliomas. The terminal prostaglandin synthases mPGES-1, mPGES-2, and cPGES convert PGH2 into prostaglandin E2. The inhibition of their function could significantly reduce PGE2 levels in tumors while avoiding some side effects related to the inhibition of the upstream enzymes COX-1 and COX-2. In this study, the immunohistochemical staining of mPGES-1 and, for the first time, the staining of mPGES-2 and cPGES are characterized and compared with COX-1 and COX-2 staining in the same tumor samples of 94 human gliomas. The main results demonstrate over-expression of all three proteins, including cPGES and mPGES-2 that are commonly considered noninducible, in both low- and high-grade tumors. For all three proteins, average expression in tumor cells was higher in grade III tumors than grade II tumors. The analysis showed no correlation between tumor grade and staining of tumor cells or vascular endothelium with any of the antibodies except in oligodendrogliomas where moderate correlation (linear correlation coefficient 0.6; P < 0.01) could be found between tumor grade and tumor cell staining with mPGES-1 and cPGES. In grade II tumors which recurred and were reoperated upon during the data gathering period, average expression of COX-2, mPGES-1, and cPGES was higher than in tumors that were operated on only once. Our results demonstrate the significance of all three terminal prostaglandin synthases, mPGES-1, mPGES-2, and cPGES, as a possible future target of inhibition in glioma therapy.