Introduction. The MDM2 gene plays an important role in tumorigenesis. The data on the Del1518 promoter polymorphism in the MDM2 gene have revealed associations with cancer. Material and Methods. We examined the role of the MDM2 Del1518 polymorphism through a comparison of the genotypes of 345 healthy Mexican women with those of 742 Mexican women with breast cancer (BC). Results. The genotype frequencies of the MDM2 Del1518 polymorphism in controls and patients with BC were 64% and 55.5% for ins/ins, 32% and 31.5% for ins/del, and 4% and 13% for del/del, respectively. The obtained odds ratio (OR) was 3.26, with a 95% confidence interval (95% CI) of 1.86-5.72 and p=0.0001, for the del/del genotype. An association was evident when we examined the distribution of the del/del genotype in patients with elevated levels of transaminase SGPT (OR=2.268; 95% CI=1.40-3.65; p=0.0001). Additionally, we observed an association of the genotypes del/del - ins/del in menopausal patients with BC with the following characteristics: tobacco consumption (OR = 1.93, 95% CI = 1.07-3.4, p=0.025), pregnancy loss (OR=2.44, 95% CI=1.37-4.35, p=0.0024), obesity (I-IV) (OR=1.8, 95% CI=1.1-2.9, p= 0.018), and elevated serum glucose levels (OR=3.72, 95% CI=2.0-6.85, p=0.0001). Conclusions. The MDM2 Del1518 polymorphism was associated with BC susceptibility, particularly in menopausal patients with BC who reported tobacco consumption, pregnancy loss, obesity and high glucose levels in the analyzed Mexican population.