X-ray repair cross-complementing 1 gene (XRCC1) is one of the most studied genes in cancers. It is significantly associated with an increased risk of breast cancer. However, XRCC1 gene polymorphism significantly varied among different ethnic groups. Objective: To evaluate the relationship between XRCC1 (Arg194Trp) polymorphism, and breast cancer risk, outcome, and treatment response using adjuvant therapy in Egyptian premenopausal females. Methods: This case-control study included 2 groups. Group A (the control group) included 50 healthy females. Group B: included 50 premenopausal females with breast cancer. All patients performed tumor marker (CA 15-3) measurement, histopathological analysis, and immunohistochemistry for BRCA1. Restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) was performed for the detection of XRCC1 (Arg194Trp) polymorphism. Results: In breast cancer cases, T allele carriers were significantly more than C allele carriers. In addition, there was a statistically significant increase in CA 15-3 level among T allele carriers of breast cancer cases than C allele carriers (P=0.04). Moreover, BRCA1 expression was significantly higher among T allele carriers compared to C allele carriers in breast cancer tissues (P=0.03) Conclusion: Our results suggested that the XRCC1 (Arg194Trp) polymorphism may be considered a predictive factor associated with the risk of occurrence of breast cancer among Egyptian premenopausal females.