Several lifestyle factors play a significant role in determining an individual's risk of breast cancer. Many of them could be modified to protect against the malignancy. A nested case-control study was conducted to examine the association between selected lifestyle factors and non-BRCA-related breast cancer risk among French-Canadian women. Some 280 women with breast cancer and who were nongene carriers of mutated BRCA gene were recruited as cases. Another 280 women, without any cancer and nongene carriers of mutated BRCA gene served as controls. A tested lifestyle questionnaire was interviewer administered to incident cases to obtain information on weight history, smoking, physical activity, and other lifestyle risk factors. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated in logistic regression models. Comparing cases to controls, breast cancer risk was higher among subjects who reached their maximum body mass index (BMI) at an older age (>50 years) (OR = 2.83; 95% CI: 2.34-2.91). A positive association was noted between breast cancer risk and weight gain of >34 lbs compared to weight gain of </=15 lbs, since the age of 20 (OR = 1.68; 95% CI: 1.10-2.58). Weight gain of >24 lbs compared to weight gain of </=9 lbs, since the age of 30 also resulted in the same relationship (OR = 1.96; 95% CI: 1.46-3.06). Similarly, since the age of 40, weight gain of >12 lbs compared to weight gain of </=1 lb was associated with increased breast cancer risk (OR = 1.91; 95% CI: 1.53-2.66). Women who smoked >9 pack-years of cigarettes had a 59% higher breast cancer risk (P = .05). Subjects who engaged in >24.8 metabolic-equivalent- (MET-) hours per week compared to </=10.7 MET-hours per week of moderate physical activity had a 52% (P = .01) decreased risk and total physical activity between 16.2 and 33.2 MET-hours per week compared to </=16.2 MET-hours per week, resulted in a 43% (P = .05) lower risk of breast cancer. In conclusion, weight history did affect breast cancer risk. Moreover, smoking appeared to raise the risk, whereas moderate physical activity had a protective effect.