A 27-year-old man complaining of cough was admitted to our hospital because of a giant mediastinal tumor on the chest radiograph. Chest CT and MRI revealed a giant polycystic mediastinal tumor. Chest radiographs on admission showed left pleural effusion due to perforation of the cyst. Laboratory data showed high serum and pleural fluid concentrations of CA 125, CA 19-9, SLX and others. The mediastinal mass was resected and diagnosed pathologically as a mature teratoma. It is reported that patients with mediastinal teratomas often have pleural fluid as a result of self-digestion by pancreatic enzymes, and some mediastinal teratomas have high serum tumor marker levels. We suspected that the high serum tumor marker levels in our case were caused by the high concentrations of tumor markers in the pleural fluid. We suggest that serum tumor marker levels may be useful in the preoperative differential diagnosis of anterior mediastinal cystic tumors.