We report a case of paraneoplastic encephalitis associated with anti-Ma2 antibodies. Medical history and thorax computed tomography findings suggested malignant mesothelioma. Pleural biopsy results were compatible with high-grade neoplastic infiltration. Although the biopsy could not differentiate the type of neoplasm, mesothelioma was considered a strong possibility in this poorly differentiated lung carcinoma. To the best of our knowledge this is the first case report of paraneoplastic encephalitis associated with anti-Ma2 antibodies and mesothelioma.