Background: Increased serum resisitin levels act as an effective pro-inflammatory mediator, which may play a key role in cancer progression and promotion and may be caused by RETN gene polymorphisms. Aim of the work: We investigated serum resistin levels in breast cancer patients as well as the relationship between the RETN single nucleotide polymorphisms (rs7408174 and rs3219175) and breast cancer susceptibility. Subjects and Methods: This case control study included 80 breast cancer patients and 80 healthy controls. Genotyping of RETN rs7408174 and rs3219175 gene polymorphism were determined by real time polymerase chain reaction (RT-PCR) TaqMan allelic discrimination assay. Serum resistin levels were quantified using Enzyme-linked immunosorbent assay (ELISA). Results: Breast cancer patients had higher serum resistin levels compared to healthy controls. Patients with rs3219175 AG and rs7408174 CT/CC genotypes had significantly higher serum levels of resistin. Carriers of the single nucleotide polymorphism (SNP) rs3219175 heterozygous (AG) and homozygous (AA) genotypes had a significantly higher breast cancer risk than carriers of the wild (GG) genotype (Odd ratio (OR): 2.437; 95% CI: 1.262-4.707 and 3.091; 0.723-13.222, respectively). Patients carrying rs3219175 AG/AG+AA and rs7408174 CT/CC genotypes had a higher risk of developing advanced tumour size (T3+T4), lymph node (LN) infiltration, and advanced TNM stage (III+IV). Conclusion: There is a strong link between RETN SNP rs3219175 and high serum resistin levels and the risk of breast cancer. Furthermore, the RETN SNPs rs3219175 and rs7408174 are linked to poor clinicopathological status.