Dietary fat is a likely important determinant of postmenopausal breast cancer as part of an intricate and inseparable interaction of lifestyle cancer risk factors that include dietary fat, type of fat, energy intake and expenditure, and obesity. These factors possibly build upon individual susceptibilities derived from a complex array of polygenetic risk determinants. Epidemiologic studies have not provided conclusive evidence for a dietary fat-breast cancer association, partly because studies that focus on a single nutrient cannot always evaluate readily the interactive effects of other lifestyle factors. Further, persons generally underestimate their usual dietary intake, measured by either food frequency questionnaires (FFQs) or diet records. A dietary measurement model that accounts for this underreporting demonstrated that FFQs and diet records may not be able to detect a dietary fat-breast cancer association because of measurement error biases. Although meta-analysis of epidemiologic data across individual studies suggests only a week association between breast cancer and dietary fat, this result is compatible with the dietary measurement model and does not rule out a contributing role for dietary fat, either alone or with other causative factors. Research is needed that focuses on a comprehensive approach to dietary lifestyle choices and breast cancer risk and that emphasizes a fat-caloric intake-obesity linkage. The best hope for a definitive answer may rest with randomized, controlled clinical trials. Two such trials, the Women's Health Initiative and the Women's Intervention Nutrition Study, are under way.