Cyclical mastopathy (CM) is a common clinical syndrome of premenstrual breast swelling and tenderness. Its symptoms are relieved by reduction in dietary fat intake and, because fat intake may be associated with breast cancer risk, it was hypothesized that CM may also be related to breast cancer risk. This case-control study included 192 premenopausal women with a recent history of axillary node-negative breast cancer and 192 age-matched premenopausal controls. Subjects provided information on diet and risk factors, and they recorded breast symptoms prospectively during one menstrual cycle. Symptoms in the noncancerous breast of cases and the matched (right or left) breast of controls were examined. A cyclical pattern of symptoms was identified in both groups; breast tenderness scores were similar postmenstrually (p = 0.31) but were significantly higher premenstrually in the case group (p = 0.03). Cases also had a greater premenstrual increase in breast tenderness than controls (p = 0.03). When the effects of other risk factors for breast cancer were included in multivariate analyses, the association of cyclical tenderness with breast cancer persisted (p = 0.05), the odds ratio for severe tenderness being 3.32. Thus, we have identified an association of cyclical breast tenderness with breast cancer risk in premenopausal women. The association persists after consideration of diet and the effects of other breast cancer risk factors.