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Skin injury is a common side effect of breast- cancer radiation therapy. Although physicians often observe skin toxicity, quantifying its severity remains a challenge. We present a novel quantitative ultrasonic technique to evaluate skin changes associated with radiotherapy. An in vivo study with twelve breast- cancer patients was conducted. All patients received a standard course of post-surgery radiation therapy. Each patient received ultrasound scans to the irradiated breast and the untreated (contra-lateral) breast. Radio-frequency (RF) backscatter signals and B-mode images were acquired simultaneously. To quantify the severity of skin injury, two metrics were calculated from the RF signals: skin thickness and Pearson correlation coefficient of the subcutaneous layer. Comparing to the non-irradiated skin, the average thickness of the irradiated skin increased by 40% (p=0.005) and the average correlation coefficient of the irradiated hypodermis decreased by 35% (p=0.02). This study demonstrates the feasibility of using a non-invasive ultrasonic technique to detect and quantify radiation-induced skin changes.