OBJECTIVE To evaluate the natural history of nonpalpable interval breast cysts detected at mammography and diagnosed at sonography in an asymptomatic female population. METHODS The imaging records of 5,000 consecutive patients (aged 35-77 years [mean, 51 years]) seen in one breast center over a 6-month period were reviewed. Serial studies of those patients with documented evidence of interval benign breast cysts were evaluated for the subsequent course of such lesions with regard to regression, stability, or enlargement seen at mammography. RESULTS Interval cysts were found in 53 patients (68 cysts), approximately 1% of the studied population. More than half of these lesions spontaneously regressed in 1 year, most of them completely. By 2 years, nearly two-thirds had regressed. By 5 years, only 12% of the lesions had not shown regression. CONCLUSIONS Interval breast cyst formation is not uncommon, and most of these benign lesions will undergo spontaneous regression or remain stable. Further intervention is not required for interval benign cysts.