Recent studies have examined the role of cyclooxygenase-2 (Cox-2) expression in normal pituitaries and pituitary adenomas and have suggested a role for Cox-2 in the regulation of angiogenesis in the pituitary. Thromboxane synthase (TBXAS), which catalyzes the synthesis of thromboxane A2, is one of the downstream enzymes in Cox metabolism and appears to play a role in the regulation of invasiveness and angiogenesis in some neoplasms. To analyze the role of Cox-2 and TBXAS in pituitary tumor progression, we examined normal pituitaries (n = 8), pituitary adenomas (n = 174), and pituitary carcinomas (n = 7) for expression of Cox-2 and TBXAS by immunohistochemistry. Weak Cox-2 and moderate TBXAS expression was present in normal pituitary cells. Most pituitary adenomas showed increased expression of both Cox-2 and TBXAS. Pituitary tumors as a whole, but particularly carcinomas, showed greater Cox-2 expression than did normal pituitaries. Pituitary adenomas and carcinomas also showed greater staining for TBXAS when compared to normal pituitary. Nonfunctional adenomas had significantly higher levels of TBXAS expression compared to functional adenomas (p = 0.017). Adenomas and carcinomas showed similar degrees of staining for TBXAS. In summary, TBXAS appears to be one of the up-regulated downstream enzymes of Cox metabolism in pituitary tumors. Both Cox-2 and TBXAS may play an important role in pituitary tumor development and progression.