Background: Breast cancer is the most common cancer in females, both in developed and developing countries. Pakistan has the highest breast cancer incidence rate in Asia. Guidelines recommend screening for detecting breast cancer with mammography and ultrasonography (US). Shear-wave elastography (SWE) is a newer technique that can aid additional characterization of breast lesions. Objective: The aim of this study was to determine the diagnostic accuracy of breast ultrasound elastography in differentiating benign from malignant breast lesions using histology diagnosis as the gold standard.Materials and methods: The study was conducted at the Abbasi Shaheed Hospital and Jinnah Post Graduate Medical Centre, Karachi. All consecutive patients undergoing breast biopsy and elastography of breast lesions were enlisted; 2 x 2 tables were used to measure the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of breast ultrasound elastography for differentiation of benign from malignant breast masses.Results: A total of 155 female patients were included with a mean age of 45.41 ± 14.24 years (range 20-70 years). On histological evaluation, 115 (74.2%) lesions were malignant and 40 (25.8%) were benign. The overall average mean elastography value was 108.45 kPa ± 52.75. The mean elastography (EMean) value for benign breast lesions was 48.96 kPa ± 42.32 and 132.78 kPa ± 42.32 for malignant lesions. The difference in mean elastography values of benign and malignant breast lesions was statistically significant (48.96 kPa ± 42.32 vs 32.78 kPa ± 42.32, P <0.001). The area under the curve (AUC) was 0.952, optimal cutoff EMean value of 72 kPa and higher likelihood ratio was 9.41. A cutoff mean elastography (EMean) value of ≤ 72 kilopascal (kPa) for benign lesions had sensitivity 92.17%, specificity 90.4%, PPV 96.36%, NPV 80.0% and diagnostic accuracy 91.61%. Conclusion: Ultrasound elastography was found to have high sensitivity and specificity and diagnostic accuracy for differentiating benign from malignant breast lesions. Use of shear-wave elastography may increase malignancy detection rate by reducing the need for biopsy in benign breast lesions.