True cysts of the spleen are rare. In a few cases, high serum levels of carbohydrate antigen (CA) 19-9 and carcinoembryonic antigen (CEA) have been reported. It has been suggested that they are produced by inner epithelium of the cyst. In such instances, cyst resection or splenectomy is indicated to rule out malignant lesions and to remove cancer antigen-producing epithelium. Furthermore, a high serum level of interleukin (IL)-10, an immunosuppressive cytokine, has been described in many neoplastic diseases, suggesting it as a potential new diagnostic method. Giant cystic lesion of the left upper abdomen associated with ovarian tumor was diagnosed in a young patient. Laboratory data revealed elevated serum levels of several tumor markers [CA 19-9, CEA, cancer antigens (CA) 125 and 50, and tissue polypeptide antigen]. In contrast, IL-10 serum level was normal. After splenectomy and ovariectomy, tumor marker serum levels normalized. Histology and immunohistochemical analysis revealed true splenic cyst with inner epithelium strongly positive for CA 19-9, CEA, and high levels of cancer antigens in fluid. Ovarian lesion was a serous cystoadenoma; its inner epithelium showed no immunoreactivity for tumor markers that were not measurable in fluid. The reported case showed that epithelium lining true splenic cysts may produce, in addition to CA 19-9, CEA, and other tumor markers, in particular CA 125 and CA 50. When malignant disease is suspected, IL-10 serum level could be useful to correctly predict the nature of the lesion.