Background: Vitamin D receptor (VDR) is a key nuclear receptor that is associated with the risk and progression of breast cancer (BC). Objectives: The present study investigated the Fok1, Bsm1, Taq1 and Cdx2 polymorphisms in the VDR gene and susceptibility to BC in a sample of Southeastern Iranian population. Methods: This case-control study was conducted on 180 women with BC and 178 age-matched healthy women. RFLP-PCR method was used for analysis of Bsm1 (rs 1544410), Apa1 (rs 7975232), Fok1 (rs 2228570) and Taq1 (rs 731236) and also TETRA-ARMS method for Cdx2 (rs 11568820). Results: No significant correlation was found between polymorphisms of Taq1, Fok1 and Apa1 with BC, but was for Bsm1 (odds ratio (OR) = 3.452, 95 CI 1.769 - 6.738; P < 0.001). Also, there was a significant correlation between the case and control groups for Cdx2 (OR = 3.720, 95 CI 2.224 - 6.225; P < 0.001) and allele A in Cdx2 had just significant correlation with BC. Conclusions: The present study findings showed that there were significant correlations between Bsm1 and Cdx2 polymorphisms with BC in women of Sistan and Baluchestan Province (southeastern Iran). Also, signals of Rs1544410-Bsm1 and Rs11568820-Cdx2 positions were difference with routes of estrogen and progesterone per person and they probably act independently. © 2017, International Journal of Cancer Management.