A splenic cyst was first described by Andral in 1829, but it is a relatively rare occurrence (1). However, recently, small splenic cysts have been occasionally observed as a result of the development of diagnostic technology. Most cysts were a symptomatic and did not require treatment. On the other hand, large splenic cysts are very rare, but they often become symptomatic and critical due to enlargement, infection, and rupture. We observed two sisters with giant symptomatic splenic cysts. Histopathologically, both cysts were epidermoid. Moreover, the serum level of CA19-9 in both sisters was high before splenectomy. The familial occurrence of splenic cysts has been reported only in five studies to date (2–6). These cases, including the ones in our report, suggest genetic changes in familial splenic cysts.