True cysts of the spleen are rare; in a few cases, high serum levels of carbohydrate and cancer antigen have been reported. In such instances, cyst resection or splenectomy is indicated to rule out malignant lesions and to remove the cancer antigen producing epithelium. We report the case of a young woman with a symptomatic giant epidermoid cyst of the spleen. Due to the secreting epithelium lining the cyst, serum levels of CA 19-9 and CA 125 were elevated. Laparoscopic splenectomy achieved symptoms relief and and long-term normalization of serum tumor markers.