We present a computer-aided diagnosis (CAD) method for breast lesions on ultrasound that is based on the automatic segmentation of lesions and the automatic extraction of four features related to the lesion shape, margin, texture, and posterior acoustic behavior. Using a database of 400 cases (94 malignant lesions, 124 complex cysts, and 182 benign solid lesions), we investigate the marginal benefit of each feature in our CAD method and the performance of our CAD method in distinguishing malignant lesions from various classes of benign lesions. Finally, independent validation is performed on our CAD method. Eleven independent trials yielded an average Az value of 0.87 in the task of distinguishing malignant from benign lesions.