We describe a unique case of brain metastases presenting as first symptom of a malignant mesothelioma (MM). MM is a highly aggressive tumor of the serous membrane that is generally believed to be rarely metastasizing. Recently, the reports of long surviving cases and larger literature reviews have suggested that cerebral metastases are not so uncommon. An extensive histochemical and immunohistochemical panel is needed to achieve a correct differential diagnosis, especially in the epithelioid type. Pathologists should be aware that brain metastases could have a mesothelial origin.