Introduction: Breast cancer is the most frequent malignancy among women worldwide. It is a multifactorial disease related to genetic, environmental and life style factors that influence the level of exposure to estrogen which may play a central role in breast cancer development. Most breast cancers are likely to be caused by low penetrance genes. CYP17 gene which encode the enzyme P450c17 alpha playing a key role in estrogen biosynthesis and ER alpha gene which play an important role in mammary epithelial cells proliferation and tumorigenesis are among this susceptibility genes. The TC substitution in the promotor region of CYP17 gene which creates a restriction site for the MspA1 restriction enzyme may lead to overexpression of this gene and higher action of the enzyme. Also, Xba1 polymorphism in the ER alpha gene may alter the activity of the ER affecting susceptibility to breast cancer.Subjects and Methods: The present study was conducted on 41 breast cancer females patients compared to a control group of 40 healthy females of matching age. Estimation of estrogen in serum (using radioimmunoassay) and detection of CYP17 and ER alpha polymorphisms (using PCR-RFLP) were performed in all patients and controls.Results: No significant association was recorded between CYP17 and ERalpha gene polymorphisms and breast cancer risk. There was a statistically significant association between ER alpha genotypes in overall breast cancer cases with each of: age at menarche, (p=0.024), age at diagnosis, (p=0.011), and nodal involvement, (p=0.037) and between nodal number and ER alpha genotypes in the premenopausal BC group, (p=0.038). Conclusion: In this study, CYP17 and ER alpha genotypes did not influence serum estradiol level. No statistically significant association was found between CYP17 -34T>C and ER alpha XbaI gene polymorphisms and breast cancer risk in Egyptian women. ER alpha gene may have an association with some clinico-pathological parameters in breast cancer in Egyptian patients.