Invasive breast cancer is a leading cause of morbidity and mortality as well as the most common malignancy among Israeli women. Over 3,800 Israeli women are diagnosed with invasive breast cancer every year and around 3400 women are diagnosed with breast carcinoma in-situ. Although smoking, either active or passive, is a controversial risk factor for breast cancer, cigarette smoking involves exposure to substrates of the NAT2 gene. The NAT2 genotype may modify the risk of cancer by activating or detoxifying heterocyclic and aromatic amines. Identification of a potential, modifiable risk factor for common and serious disease is very important for prevention and identification of high risk groups. This literature review aims to describe published studies and increase attention to measures of exposure to tobacco smoke, as well as to aspects of the NAT2 genotype that may modify the association between passive smoking and breast cancer risk. The results suggest that the NAT2 status has a differential effect on the association of active and passive smoking with breast cancer and demonstrates the need to consider possible different mechanisms associated with exposure to main and side-stream tobacco smoke. However, methodological limitations, such as small sample size, and varying definitions of smoking, are likely to have contributed to the inconsistent findings.