We evaluated the association between physical activity and breast cancer risk among 1,463 breast cancer cases and 4,862 controls in a multinational study. All subjects were asked how many times and for how long they exercised or engaged in strenuous physical labor per week. We used multivariate logistic regression to assess the association between physical activity and breast cancer risk. For all subjects combined, the multivariate-adjusted odds ratio was 50% lower (95% confidence interval = 0.4-0.6) for women who reported physical activity once per week or more after adjusting for age, race, body mass index, and pack years of smoking compared to those who reported physical activity less than once per week. Women who reported physical activity 3 times/wk or more did not gain any additional reduced risk. The amount of time spent in physical activity per session was also significantly associated with reduced risk. All ethnic groups examined including Caucasian-Americans, African-Americans, Hispanic-Americans, Tunisian-Arabs, and Polish-Caucasians were at 35% or greater reduced risk for breast cancer if they were physically active for more than 30 minutes per week. Our study shows that physical activity may reduce breast cancer risk regardless of race, weight category, or family history of breast cancer.