We investigated single nucleotide polymorphism (SNP) of the betaglycan gene () encoding the TGFβ co-receptor in endometrial cancer (EC) and its association with betaglycan expression. The study group included 153 women diagnosed with EC and 248 cancer-free controls. SNP genotyping and gene expression were analyzed using TaqMan probes. Three out of the eight SNPs tested, i.e., (CT; OR = 2.22; 95% CI = 1.15-4.30; = 0.0177), (GC; OR = 2.34; 95% CI = 1.20-4.53; = 0.0120) and (TT; OR = 6.40; 95% CI = 1.18-34.84; = 0.0317) were found to be significantly associated with increased risk of EC (adjusted to age, body mass index, menarche and parity). Among the analyzed SNPs, only demonstrated the impact on the increased cancer aggressiveness evaluated by the WHO grading system (G3 vs. G1/2, GT-OR = 4.04; 95% CI = 1.56-10.51; = 0.0026; T-OR = 2.38; 95% CI = 1.16-4.85; = 0.0151). Linkage disequilibrium (LD) analysis revealed high LD (r2 ≥ 0.8) in two haploblocks, constructed by / and /, respectively. In the case of C/C haplotype (OR = 4.82; 95% CI = 1.54-15.07; = 0.0116-Bonferroni corrected) and T/G haplotype (OR = 3.25; 95% CI = 1.29-8.15; = 0.0328-Bonferroni corrected) in haploblock /, significantly higher frequency was observed in patients with EC as compared to the control group. The genotype-phenotype studies showed that SNPs of the 3 gene associated with an increased risk of EC, i.e., and may affect betaglycan expression at the transcriptomic level (-CC vs. TT, < 0.01; -GG vs. TT, < 0.001, GT vs. TT, < 0.05). Functional consequences of evaluated 3 gene SNPs were supported by RegulomeDB search. In conclusion, polymorphism of the 3 gene may be associated with an increased EC occurrence, as well as may be the molecular mechanism responsible for observed betaglycan down-regulation in EC patients.