We report a giant splenic epithelial cyst which produced carbohydrate antigen 19-9 (CA 19-9) in a 21-year-old woman with left abdominal pain. Imaging techniques revealed a huge cyst of the spleen, and laboratory data revealed elevated serum CA 19-9 (830 U/ml; normal, < 27 U/ml). After splenectomy, serum CA 19-9 level returned to normal. A unilocular splenic cyst measuring 16 x 14 x 13 cm contained brown fluid (900 ml) with a high level of CA 19-9 (10,150,000 U/ml). The wall of the splenic cyst was composed of inner stratified epithelium with mixed squamous and columnar differentiation; immunohistochemical analysis showed that the epithelial cells of the cyst showed strong immunoreactivity to CA 19-9. The inner connective tissue of the cyst wall devoid of epithelial cells was also strongly positive for CA 19-9. We suggest that epithelial cells of our splenic epithelial cyst produced a large amount of CA 19-9 which diffused into capillaries of the connective tissue of the cyst wall and entered into systemic circulation, resulting in the elevated serum CA 19-9.