Epidemiological studies show a lower frequency of fibrocystic breast disease among long-term users of oral contraceptives than among women who have never used them. Fibrocystic disease may be a precursor of breast cancer; yet the incidence of breast cancer does not appear to differ between pill-takers and nontakers. To resolve this conflict, we examined the problem from a histologic standpoint in 205 premenopausal women, and found that this decreased frequency applied only to fibrocystic disease in which epithelial atypia was minimal or absent. In women with marked atypia there was no significant difference in frequency among long-term users as compared to women who have never used oral contraceptives. These findings suggest that a spectrum of cystic disease exists and that the long-term use of oral contraceptives protects against the forms of fibrocystic disease that are not firmly associated with an increased risk of breast cancer, but not against the premalignant forms.