The authors examined the association of fatal breast cancer and cigarette smoking in a large, prospective mortality study of US adults. After 6 years of follow-up, 880 cases of fatal breast cancer were observed in a cohort of 604,412 women who were cancer-free at interview in 1982. Cox proportional hazards modeling, adjusted for other risk factors, found that current smoking was significantly related to fatal breast cancer risk (adjusted rate ratio (RR) = 1.26, 95% confidence interval (CI) 1.05-1.50). A negative association was observed for former smokers, but this was not statistically significant (RR = 0.85, 95% CI 0.70-1.03). The association of current smoking with fatal breast cancer risk increased with increasing numbers of cigarettes per day and with total number of years smoked. For smokers of 40 or more cigarettes per day, the rate ratio was 1.74 (95% CI 1.15-2.62). The authors hypothesize that these results may be due to either a poorer prognosis among breast cancer cases who smoke or a delayed diagnosis among current smokers who do not receive mammograms as often as never or former smokers. Women who smoke should be targeted for breast cancer screening services.