The role of osteopontin as a biomarker in endometrial cancer has not been conclusively established. We evaluated the expression and potential of osteopontin as a biomarker for endometrial cancer. Real-time polymerase chain reaction and immunohistochemistry revealed osteopontin overexpression in endometrial cancer. The plasma osteopontin level in endometrial cancer was significantly higher than in healthy controls (P< 0.001). In FIGO stage I endometrial cancer, osteopontin correctly identified 18 of 29 cases (62.1%) that were not detected by CA125. By Cox multivariate analysis, osteopontin positivity was an independent prognostic factor for disease-free survival (hazard ratio = 3.18, P= 0.035).