The T-cell immunoglobulin and mucin domain containing molecule 3 (TIM-3) gene is an important immune regulatory molecule. In fact, studies have shown that polymorphisms in the (TIM-3) gene may be associated with various cancers. The goal of this study was to investigate whether the -1516G/T, -574G/T, or +4259T/G single-nucleotide polymorphisms (SNPs) in the TIM-3 gene contribute to a genetic susceptibility to invasive breast cancer in the Han ethnicity of northern China. Genotyping of the TIM-3 -1516G/T, -574G/T and +4259T/G were performed in 301 patients with invasive breast cancer and in 151 healthy individuals via a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The results showed that the prevalence of the +4259T/G genotype and the +4259G allele were significantly increased in the breast cancer patients compared to the controls [odds ratio (OR)=7.641, 95% confidence interval (CI), 1.795-32.522, P=0.001; OR=7.317, 95% CI, 1.731-30.925, P=0.001, respectively]. The GGG haplotype had a significantly different distribution between patients and controls (OR=5.421, 95% CI, 1.263-23.275, P=0.011). In addition, the prevalence of the +4259T/G polymorphism was higher in patients with metastasis than those without metastasis (13.6% vs. 4.8%, respectively, OR=3.158, 95% CI, 1.300-7.672, P=0.011). Furthermore, results showed that the prevalence of the +4259T/G genotype was correlated with the intensity of Ki-67 by immunohistochemical staining (P=0.022). Overall, these results suggested that the +4259T/G SNP in the TIM-3 gene may play an important role as a genetic risk factor for the progression and prognosis of invasive breast cancer in these patients. in Han ethnicity of northern China.