This prospective single-center study enrolled 50 women with 51 contrast-enhanced mammography (CEM)-enhancing lesions that lacked a sonographic or mammographic correlate. Trial participants underwent CEM-guided biopsy. Biopsy was technically successful for 46 lesions and was not performed for five nonvisualized lesions (all nonmass enhancement), yielding a cancellation rate of 9.8%. Mean biopsy time was 16.6 minutes. All biopsies revealed concordant pathology (25 benign, 10 high-risk, 11 malignant). No non-visualized or benign lesion yielded malignancy at follow-up.