Background: Estrogen receptor (ER) and vitamin D receptor (VDR) is a ligand-activated transcription factor that mediates estrogen and vitamin D actions in target tissues. Several common polymorphisms of the ER- αgene and VDR gene have been reported to be associated with alterations in receptor expression and function. Objective: We evaluated the hypothesis that genetic polymorphisms in the PvuII restriction site of ER- α gene and FokI restriction site of VDR may be associated with breast cancer risk in Egyptian. Methods: In this study the involvement of two RFLPs, one at the ER-α gene locus, denoted as PvuII and the other at the VDR gene denotes as FokI in breast cancer were examined in 50 breast cancer cases and50 age frequency-matched controls. A case-control comparison was performed and the genotype distributions examined according to different tumor and population parameters. Result(s): PvuII polymorphism was associated with an increased risk of breast cancer (OR = 1.9 (0.75 5.0), P=0.01), while there was no significant difference in genotype frequency of the FokI polymorphism between controls and cases . In addition, significant association was found in patients with LN metastasis carrying the ER –α PvuII polymorphism. Also this study showed non-significant but generally higher relative risk of breast cancer for the f allele carriers of FokI polymorphism of Vitamin D receptors gene with breast cancer risk (OR =2,65(1.5- 5.2) P=0.000). We did not find significant association between ERs gene PvuII res polymorphism and VDRs gene FokI polymorphism however there is significant association between the f allele and the p allele in cases (P=0.02). Conclusion(s): These results suggest that biomarkers for genetic polymorphisms could be used for the identification of breast cancer risk among Egyptian women.