Brain metastases represent an uncommon complication in malignant pleural mesothelioma. A 55-year-old male suffering from malignant mesothelioma and pretreated with intracavitary chemotherapy and radiotherapy was submitted to systemic chemotherapy including lomustine, carboplatin, vinorelbine, fluorouracil and folates after diagnosis of bilateral cerebral deposits. The patient had an impressive response to chemotherapy, with complete regression of related symptoms. This case report represents the first on response to chemotherapy of brain metastases from mesothelioma. It points out that chemotherapy should be further explored in this subset of patients.