Ultrasound is a complementary imaging modality for detection of mammographically occult breast cancers, especially in patients with dense breast tissue. Diagnostic accuracy of ultrasound in these patients can be significantly improved using contrast agents targeted at molecular signatures on the tumor neovasculature. In a large scale immunohistochemcical staining analysis of human tissues, it was found that B7-H3 is differentially expressed in breast cancer–associated vascular endothelial cells compared with normal, benign, and precursor lesions. Also, B7-H3-targeted ultrasound molecular imaging allowed detection of breast cancer in a transgenic mouse model of breast cancer development. For details, see article by Bachawal and colleagues on page 2501.