Background: Tobacco use has been implicated in the etiology of a large number of cancers, and there exists substantial biological plausibility that it could also be involved in breast carcinogenesis. Despite this, epidemiological evidence to date is inconsistent. The aim of this study was to investigate the role of active smoking and the risk of incident, invasive breast cancer using a prospective cohort of women from the Canadian Study of Diet, Lifestyle and Health. Methods: Using a case-cohort design, an age-stratified subcohort of 3314 women was created from 39,532 female participants who returned completed self-administered lifestyle and dietary questionnaires at baseline. A total of 1096 breast cancer cases were identified in the entire cohort (including 141 cases from the subcohort) by linkage to the Canadian Cancer Registry. Cox regression models were used to estimate hazard ratios for the association between the different smoking exposures and the risk of breast cancer, using a modification for the case-cohort design. Results: After carefully considering early-life exposures and potential confounders, we found no association between any smoking exposure and risk of breast cancer in this study (Hazard ratio. = 1.00, 95% confidence interval. = 0.87-1.17 for ever vs never smokers). Conclusions: Although these results cannot rule out an association between smoking and breast cancer, they do agree with the current literature suggesting that, if an association does exist, it is relatively weak.