Background: Endometrial cancer is a common gynecological malignancy with good prognosis in the early stages of the disease. The CpG island in the promoter region of tumor-suppressor genes are frequently methylated in various types of human cancers. In the present study, we have examined the methylation status of the p16INK4a and p14ARF genes in endometrial cancer and healthy endometrium with the aim to identify correlations between promoter hypermethylation, disease risk, and clinicopathological parameters.Methods: We collected 28 formalin fixed paraffin embedded samples and 26 blood samples from endometrial cancer patients and 22 controls. Methylation-specific PCR was applied to analyze the promoter methylation status of the p16INK4a and p14ARF genes in the studied population. The results were analyzed with SPSS software version 20.Results: There was a significant difference between the study groups and the presence of promoter CpG hypermethylation status in the p14 (P<0.0001) and p16 (P<0.05) genes. p14 hypermethylation in the blood samples was associated with depth of myometrial invasion in endometrial cancer (P=0.03). A significant association existed between p16methylation in tissue with endometrial cancer grade (P=0.06). No statistically significant difference existed between the p16INK4a and p14ARF promoter hypermethylations in blood (P=0.177) and formalin fixed paraffin embedded (P=0.221) samples. An association existed between p16INK4a and p14ARF gene hypermethylations in blood and tissue with diabetes.Conclusion: Our results have confirmed that epigenetic mechanisms play an important role in endometrial cancer incidence. They can be utilized as prognostic biomarkers for endometrial cancer. The lack of a significant difference between the p16INK4a and p14ARF promoter hypermethylations in blood and formalin fixed paraffin embedded samples has indicated that methylation status of a blood sample can be an early, non-invasive diagnostic marker in endometrial cancer.