Aim: DNA methylation testing for endometrial cancer detection in minimally invasive specimens is a promising tool to improve screening and diagnostic procedures. Available literature was systematically reviewed to assess the potential of this approach and define methylation markers deserving further development. Methods: A systematic search up to March 31 2020 was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: 15 methylation markers with an area under the curve value of ≥ 0.80 for endometrial cancer detection in cytological specimens were selected from nine studies. Conclusion: Detection of methylation markers in cytological samples indicate the feasibility of minimally invasive testing methods, potentially guiding diagnosis and detection of endometrial cancer in high-risk women and in cancer screening programs.