Abstract: To study the diagnostic and prognostic values of serum YKL-40 in endometrial cancer. Methods: Serum YKL-40 levels were detected and compared in 34 of 50 cases with endometrial cancer ( EC ) before surgery, in 22 of the 34 EC cases after surgery, in 30 cases with uterine myoma, and in 30 healthy female subjects as normal controls. Receiver operating characteristic ( ROC ) curves were adopted for diagnosis and calculation of the area under each ROC curve in EC. The progression-free survival ( PFS ) and overall survival ( OS ) between the YKL-40 positive and negative patients were compared in the follow-up. Results: The mean preoperative serum YKL-40 value was ( 158.49±80.39 ) μg/L in the EC patients, which was significantly higher compared with ( 62.9±25.88 ) μg/L in the uterine myoma cases and ( 52.8±26.90 ) μg/L in the healthy subjects ( P = 0.000 ). The mean postoperative serum YKL-40 level in the 22 EC cases ( 165.12±96.9 ) μg/L was significantly lower than the preoperative serum YKL-40 level in these cases ( 120.91±92.77 )μg/L ( P = 0.000 ). The areas under the ROC curve were 0.807 and 0.667 for YKL-40 and CA125, respectively ( P = 0.053 ). There were critical differences between the two ( P = 0.053 ), namely, the PFS and OS for the YKL-40-positive patients ( 13 and 18 months, respectively ) were significantly shorter than those for the YKL-40-negative patients ( 16 and 22 months, respectively ), considering the value of YKL-40 106.6 μg/L as the upper normal limit. The Log-rank test results also showed statistically significant differences between the two. Conclusion: Preliminary investigations have shown that serum YKL-40 level may have a definite clinical value in the diagnosis and prognosis of EC.