Splenic cysts are relatively rare entities. The differential diagnosis for these lesions includes parasite infections, results of previous trauma or infarction, congenital forms, primitive splenic neoplasm or cystic metastasis. They can be either symptomatic, causing mainly abdominal pain, or asymptomatic, thus being diagnosed as in incidental finding during radiological examination for other clinical reasons: among these a raised serum level of CA 19-9 can be a case. It has been demonstrated that epidermoid and mesothelial congenital cyst can be associated with a pathological level of this tumor marker which is usually correlated to biliopancreatic and colonic carcinomas. The aim of the present study is to present the case of an asymptomatic epidermoid splenic cyst associated with a continuous increase of CA 19-9 and to describe the applied clinical workup and surgical management by laparoscopic total splenectomy. Moreover, to analyze the demographics, clinical and pathological features of these infrequent lesions and to confront our therapeutic management with that of the other reported cases, we conducted a systematic review of the literature.