Significant efforts have been made to dissect the molecular pathways involved in the carcinogenesis of thymic malignancies. Research is hampered by the rarity of the tumor, controversies about histopathologic classification, and the lack of established cell lines and animal models. Insights into the biology of these tumors have been made following anecdotal clinical responses to targeted therapies. This article reviews current knowledge about the molecular data that define molecular subsets and support the use of targeted therapies in thymic tumors.