A 5-month-old boy who was diagnosed as having hydrops fetalis at 25 weeks' gestation had severe ascites of unknown origin. At the age 12 months, ultrasonography and computed tomography showed multiple cysts in the spleen that were increasing in size rapidly. Splenectomy resulted in complete disappearance of the ascites. These cysts were diagnosed as mesothelial cysts because the cell lining of the splenic cysts stained positively with alcian blue and cytokeratin. The boy's mother had undergone splenectomy for splenic and retroperitoneal lymphangiomas at 4 years of age. Histological reevaluation showed that the lining of her splenic cysts had the same mesothelial components as her son's. Their chromosomal assay showed normal karyotypes. Mesothelial cyst of the spleen appears similar to splenic lymphangioma morphologically; however, bleomycin and OK-432 were not effective. Familial splenic mesothelial (epidermoid) cysts have been reported in three sets of siblings, but this is the first report of their occurrence in mother and son.