To examine whether dietary fiber modifies breast cancer risk, a case-control study involving 351 newly diagnosed patients with breast cancer and 356 hospitalized controls was conducted in Uruguay. Dietary patterns were assessed in detail by use of a food frequency questionnaire on 64 items, which allowed the calculation of total energy intake. Nutrient residuals were calculated through regression analysis. After adjustment for potential confounders (which included age, residence, family history of breast cancer, prior history of benign breast disease, parity, total energy, red meat, lutein/zeaxanthin and quercetin intake, and menopausal status), dietary fiber and total nonstarch polysaccharides were associated with a strong reduction in risk of breast cancer (odds ratio for uppermost quartile of total dietary fiber = 0.51, 95% confidence limit = 0.31-0.82). Also the dose-response pattern was highly significant (p < 0.001). The inverse association was observed in pre- and post-menopausal women and was similar for soluble and insoluble fiber. Furthermore, dietary fiber displayed a strong joint effect with fat, quercetin, and lutein/zeaxanthin.