We report a young woman with a large, calcified anterior mediastinal mass discovered 18 months following a left talc pleurodesis. The lesion was evaluated and treated as the thymoma or teratoma that it appeared to be, with excision by a transcervical approach. Pathologic examination revealed a giant talc granuloma. Awareness of such a possibility following talc pleurodesis may allow surgeons to avoid unnecessary mediastinal exploration, and its occurrence suggests that talc administration simultaneous with mechanical pleurodesis should be avoided.