Objective. To evaluate the efficacy of contrast-enhanced power Doppler sonography in the differential diagnosis of breast lesions after a mammography-gray scale sonography combination. Methods. Sixty-eight patients with 69 breast masses underwent power Doppler sonography before and after intravenous injection of a contrast agent. The lesions were diagnosed as "highly suggestive of malignancy" (category 5; n = 32), "suspicious" (category 4; n = 21), and "probably benign" (category 3; n = 16) by mammography and gray scale sonography, modeled on the American College of Radiology Breast Imaging Reporting and Data System classification. Power Doppler findings did not affect patient treatment. The authors subjectively evaluated the estimated area of vascularity, degree of enhancement following contrast agent administration, morphologic features, and distribution of vessels within the lesions. Results. The final diagnoses were malignant in 28 lesions and benign in 41. Significant enhancement after contrast agent injection was detected in both the malignant and benign groups. Only 2 criteria, estimated area of vascularity and degree of enhancement following contrast agent administration, proved to be significant diagnostic determinants for contrast-enhanced power Doppler sonography (P < .001; interobserver agreements, 74.4 and 77.8, respectively). Contrast-enhanced power Doppler sonography provided a higher specificity, positive predictive value, and negative predictive value than power Doppler sonography but a lower sensitivity and negative predictive value than mammography-gray scale sonography. Only in the category 4 lesions could the combination of mammography-gray scale sonography and contrast-enhanced power Doppler sonography accomplish a higher specificity (71 %) and positive predictive value (70%) than mammography-gray scale sonography (39% and 53%, respectively). Conclusions. Power Doppler and contrast-enhanced power Doppler sonography cannot be recommended as confirmatory tests in Breast Imaging Reporting and Data System category 3 and category 5 lesions. Although contrast-enhanced power Doppler sonography may help reduce unnecessary biopsies in Breast Imaging Reporting and Data System category 4 lesions, recommendation of its use has many drawbacks, such as imperfectly established criteria, lack of absolute certainty, and high cost.