Abstract: Compositions and methods for detection and diagnosis of breast cancer are disclosed. In particular, the invention relates to the use of B7-H3-targeted imaging agents for molecular imaging of breast cancer. Vascular expression of B7-H3 is selectively and significantly higher in breast cancer tissues. Detection of B7-H3 can be used to distinguish between benign and malignant lesions with high diagnostic accuracy. B7-H3-targeted imaging agents can be produced by conjugation of a B7-H3-binding antibody, aptamer, or other ligand to various diagnostic agents, such as contrast agents, photoactive agents, or detectable labels that are useful for detection and medical imaging of breast cancer tumors.