BACKGROUND Peritoneal mesothelioma is a rare malignant neoplasm that might be linked to chronic peritoneal inflammation. As well, the association peritoneal mesothelioma-familial Mediterranean fever is uncommon. METHODS We report the case of a 60-year-old man who presented for 30 years with standard periodic familial Mediterranean fever accompanied by acute abdominal episodes, sensitive to colchicine. Between 1988 and 1995, acute abdominal episodes were accompanied by more and more profuse recurrent ascites, partially resolving under colchicine treatment. In 1995, the last episode was severe (with loss of weight and inability to tolerate feeding) and conducted to the patient's death due to peritoneal mesothelioma, as confirmed by the biopsy. CONCLUSIONS Profuse and recurrent ascites is unusual in standard periodic familial Mediterranean fever. Asbestos exposure at the origin of peritoneal mesothelioma is not well documented. Furthermore, the disease clinical and paraclinical features are misleading, and the diagnosis is based on histology. The prognosis is severe, and treatment is usually disappointing. Our observation clearly demonstrates the interconnection between an unusual form of profuse and relapsing ascites that occurred in the course of a periodic disease and peritoneal mesothelioma. The potential role of recurrent peritonitis related to familial Mediterranean fever in the pathogenesis of the tumor is discussed.