The purpose of this study was to retrospectively evaluate the use of US elastography in the differentiation of mammographically detected suspicious microcalcifications, using histology as the reference standard. Between May 2006 and April 2007, real-time US elasticity images were obtained in 77 patients (age range, 24-67 years; mean, 46 years) with 77 mammographically detected areas of microcalcifications (42 benign and 35 malignant lesions) prior to needle biopsy. Two experienced radiologists reviewed cine clips of elasticity and B-mode images and assigned an elasticity score of 1 to 3 in consensus, based on the degree of strain in the hypoechoic lesion without information of mammography and histology. For the elasticity score, the mean +/- standard deviation was 1.5 +/- 0.7 for benign and 2.7 +/- 0.7 for malignant lesions (P < 0.001). When a cutoff point between elasticity scores of 1 and 2 was used, US elastography showed 97% (34/35) sensitivity, 62% (26/42) specificity, 68% (34/50) PPV, and 96% (26/27) NPV with an Az value of 0.852 (0.753-0.923, 95% confidence interval) in the differentiation of benign and malignant microcalcifications. Our results suggest that US elastography has the potential to differentiate benign and malignant lesions associated with microcalcifications detected at screening mammography.