ABSTRACT The aim of this study is to evaluate COMT2, COMT3, CYP1B1, and ESR1 gene polymorphisms and occurrence of endometrial polyps. In addition, we intended to evaluate the clinical and epidemiological features of patients with and without the presence of the disease, characterizing the possible risk factors. A cross-sectional study was performed, with a total of 309 women, including 236 in the group of women with endometrial polyp confirmed by hysteroscopy and anatomical pathological examination and 73 in the group of people with diagnostic hysteroscopy without abnormal findings from the macroscopic point of view. Polymorphisms of four genes were studied: COMT2 (rs4680), COMT3 (rs5031015), CYP1B1 (rs1056836), and ESR1 (rs2234693). Polymorphism genotyping was determined using real-time polymerase chain reaction. Considering the results, no differences were identified between the two groups with respect to age, body mass index, diabetes, dyslipidemia, or smoking. The group of women without endometrial polyps showed higher use of hormone therapy than the other group (16.4 percent versus 3.8 percent, p < .001). The COMT2, COMT3, CYP1B1, and ESR1 genes exhibited no significant difference for the occurrence of endometrial polyp between the two groups. The research concluded that no correlation was identified between the genetic polymorphisms evaluated and the presence of endometrial polyps.