The secreted glycoprotein YKL-40 is a member of the chitinase family and elevated serum YKL-40 levels have been reported to be associated with reduced survival in several malignancies, including endometrial cancer. This study investigated immunoreactivity to YKL-40 protein and its prognostic implications in endometrial cancer. Levels of YKL-40 protein in normal endometrium (n = 42), endometrial hyperplasia (n = 40) and endometrial adeno carcinoma (n = 68) were examined using immunohistochemistry. YKL-40 immunoreactivity was significantly higher in endometrial adenocarcinoma compared with hyperplastic and normal endo metrium. In addition, high immuno reactivity of YKL-40 protein was associated with advanced stage, high histological grade, lymph node metastasis and lympho vascular invasion. Moreover, positive immunoreactivity for YKL-40 was a significant predictor of poor prognosis, as measured by estimated progression-free survival and estimated overall survival, compared with negative immunoreactivity. In conclusion, high YKL-40 immuno reactivity in endometrial cancer may be associated with poor prognosis.