Statement of Purpose: Hydroxyapatite (HA) microcalcifications (µcals) are the most common abnormality detected in mammographic screening for breast cancer, coincident with 30-50% of all breast cancers and 85-95% of all ductal carcinoma in situ [1,2]. Mammographic screening is the gold standard for early detection of breast cancer, contributing to a 30% decrease in mortality , but mammographic sensitivity drops to 36% for women with dense breast tissue versus 98% for women with almost entirely fatty breast tissue . Moreover, dense breast tissue is independently associated with a four-to five-fold increased likelihood of developing breast cancer . Bisphosphonate-functionalized gold nanoparticles (BP-PEG-Au NPs) were recently demonstrated to enable contrast-enhanced detection of μcals that were otherwise undetectable in murine models of both normal and radiographically dense breast tissue [6,7]. However, clinical translation requires further investigation using human-scale anatomic models and clinical imaging instrumentation. Therefore, the objective of this study was to investigate contrast-enhanced mammographic detection of model μcals with BP-PEG-Au NPs in radiographic phantoms with varying breast density.