Three hundred sixty-five patients with biopsy-proven benign breast disease were followed annually in a prospective manner for 4-15 years to analyze breast cancer development, recurrence, and efficacy of management during follow-up. Eleven breast cancers developed in 11 patients during follow-up, giving a 2.6-fold increased cancer risk over the reference population. No association was found between patients who developed cancer and those who did not with respect to the initial histologic feature (p = 0.62), the age at entry by decades (p = 0.40), and relative to menopause (p = 0.54), the presence of cysts (p = 0.87), or calcification (p = 0.74) in the biopsy specimen, a family history of breast cancer (p = 0.80), or the number of observation years (p = 0.27). We conclude that an aggressive approach to benign breast disease is not justified for any type of lesion as defined in this report. Benign breast disease does not inevitably lead to recurrence. Moreover, 41% of our patients never had any recurrence and were free of symptoms during follow-up; 67% never had a mammogram and 82% never required a further operation. There was no association with initial histologic feature in patients who had clinical examination only and those who had mammogram, biopsy, or both during follow-up (p = 0.93). Mammograms were mainly used to clarify a clinical recurrence than as a screening tool, regardless of histologic feature (p = 0.76). Mammograms were mainly used in premenopausal patients (p less than 0.001) having lumps (p less than 0.001), namely, the most difficult patients for radiologic interpretation. This may be one important reason for the rather low sensitivity (75%) and specificity (40%) of mammography in this report. In conclusion, clinical examination is the outstanding investigational tool to follow patients with biopsy-proven benign breast disease, especially in young premenopausal patients.