This study prospectively assessed second-look ultrasound (US) for the evaluation of incidental enhancing lesions identified on preoperative breast magnetic resonance imaging (MRI). Between 2004 and 2007, 182 patients with malignant breast lesions detected on US and/or X-ray mammography and confirmed by cytology/histology underwent preoperative breast contrast-enhanced (CE)-MRI. Patients with incidental lesions on breast MRI underwent second-look high-resolution US directed at the site of the incidental finding. Diagnosis of incidental lesions was based on biopsy or 24-month follow-up. Breast MRI detected 55 additional lesions in 46/182 (25.2%) patients. Forty-two of 55 (76.3%) lesions were detected on second-look US in 38/46 (82.6%) patients. Malignancy was confirmed for 24/42 (57.1%) correlate lesions compared with 7/13 (53.8%) noncorrelate lesions. Second-look US depicted 8/9 (88.8%) Breast Imaging Reporting and Data System (BI-RADS) 5, 16/22 (72.7%) BI-RADS 4 and 18/24 (75%) BI-RADS 3 lesions. Sensitivity, specificity, accuracy and positive and negative predictive values for lesion detection/diagnosis was 100%, 88.9%, 94.6%, 90.3% and 100% for MRI and 64.3%, 70.4%, 67.3%, 69.2% and 65.5% for second-look US. Improved performance for US was obtained when masslike lesions only were considered. Second-look US is a confirmatory method for incidental findings on breast MRI, particularly for mass-like lesions.