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<h3>Objective.</h3> —To examine the relation between proliferative benign breast disease with and without atypical hyperplasia and the subsequent risk of breast cancer. <h3>Design.</h3> —Case-control study nested within a prospective cohort study. Median follow-up after breast biopsy was 8 years (25th to 75th percentile, 5 to 14 years). <h3>Participants.</h3> —Selected from a prospective cohort of 121 700 US registered nurses followed up from 1976 to 1986. Cases were women with breast cancer who had a prior biopsy for benign breast disease. Controls were randomly selected and matched on year of biopsy and year of birth from among women in the cohort who had a benign breast biopsy but who did not develop breast cancer. Included in the analysis were 121 cases and 488 controls. <h3>Main Outcome Measure.</h3> —Development of breast cancer. <h3>Results.</h3> —Slides from the first benign breast biopsy were reviewed by two breast pathologists blinded to the outcome. The multiply adjusted relative risks (RRs) for breast cancer, relative to women with no proliferative disease, were 1.6 for proliferative disease without atypia (95% confidence interval [Cl], 1.0 to 2.5) and 3.7 for atypical hyperplasia (95% Cl, 2.1 to 6.8). Breast cancer risk was more strongly associated with atypical hyperplasia among premenopausal women (RR = 5.9; 95% Cl, 2.9 to 13.2) than postmenopausal women (RR = 2.3; 95% Cl, 0.9 to 5.9), but the association of breast cancer risk with proliferative disease without atypia did not differ across menopausal status. <h3>Conclusion.</h3> —These results confirm the marked increase in breast cancer risk among women with atypical hyperplasia, particularly in premenopausal women, and suggest that these women should be encouraged to undergo frequent breast cancer screening. (<i>JAMA</i>. 1992;267:941-944)