The purpose of this study was to evaluate the diagnostic value of qualitative and semi-quantitative assessment of ultrasound elastography in differentiating between benign and malignant breast lesions. This prospective study was conducted in two tertiary medical centers. Consecutive B-mode ultrasound and real-time elastographic images were obtained for 67 malignant and 101 benign breast lesions in 168 women. Four experienced radiologists analyzed B-mode ultrasound alone and B-mode ultrasound combined with elastography independently. Conventional ultrasound findings were classified according to the American College of Radiology Breast Imaging Reporting and Data System classification. The elastographic assessment was based on qualitative and semi-quantitative parameters (i.e., strain pattern, width ratio, strain ratio). The sensitivity and specificity of combined elastography and conventional ultrasound were significantly higher than that of conventional ultrasound alone. The sensitivity, specificity, positive predictive value and negative predictive value was 97%, 61.4%, 62.5% and 96.8%, respectively, for conventional ultrasound and 100%, 93%, 99% and 90%, respectively, for combined technique. The semi-quantitative assessment with strain ratio and width ratio in elastography were the most useful parameters in differentiating between benign and malignant breast lesions. Cut-off point values for width ratio of more than 1.1 and strain ratio of more than 5.6 showed a high predictive value of malignancy with specificities of 84% and 76%, respectively (p