The treatment of advanced stage thymomas and thymic carcinomas is a multimodal therapy. New therapeutic targets are currently under investigation, including the epidermal growth factor receptor (EGFR) as well as KIT. A number of studies have shown protumorigenic potential of Cyclooxygenase-2 (COX-2) in a variety of human malignancies, but so far it is unknown whether COX-2 is expressed in primary malignancies of the thymus. Using tissue microarrays, the expression of COX-2, microsomal-PGES-1 and -PGES-2 (mPGES-1 and mPGES-2), as well as EGFR was evaluated in different subtypes of thymoma and thymic carcinomas. COX-2 was expressed in all subtypes as determined by immunohistochemistry. Some cases of type B2 and thymic carcinomas had COX-2 staining levels classified as mild to moderate. However, when measuring the optical color intensity, no significant differences could be detected. Concerning the expression levels, a weak correlation between the expression of COX-2, mPGES-1 and mPGES-2 as well as EGFR was found. Furthermore, additional cases of thymomas and thymic carcinomas were analyzed by COX-2 Western immunoblot analysis and were compared to normal thymi. The analysis showed that thymomas and thymic carcinomas had a significantly stronger COX-2 expression than that of the normal thymi (p < 0.04). In summary, COX-2 is expressed in all subtypes of thymomas and thymic carcinomas and thus represents, in addition to EGFR and KIT, a potential therapeutic target. Further studies are needed in order to determine whether a combined therapy using COX-2 inhibitors in addition to the evolving anti-EGFR antibody therapy may be considered as a treatment option.