In single-center trials across 42,838 examinations, 150 (0.35%) cancers were identified only sonographically in average-risk women. Over 90% of the 126 women with sonographically depicted cancers had dense or heterogeneously dense parenchyma. Of the 150 cancers, 141 (94%) were invasive, with a mean size of 9 to 11 mm across the series. Over 90% were node-negative. A3-year multicenter trial of screening sonography in high-risk women, blinded to the results of mammography, opened for enrollment April 2004,funded by the Avon Foundation and National Cancer Institute through the American College of Radiology Imaging Network (ACRIN Protocol 6666). If the trial is successful,the results will provide a rational basis for supplemental screening sonography in women with dense breasts.