Breast cancer is the most common form of cancer among women globally and the second leading cause of cancer-related deaths among women in the United States. Microcalcifications (μcals) are the most commonly detected abnormality in the diagnosis of breast cancer. However, the detection of μcals and other breast lesions can be obscured by radiographically dense breast tissue. The radiographic density of breast tissue varies between women depending on the relative amounts of low-density adipose tissue and high-density fibroglandular tissue. Therefore, the overall objective of this study was to develop an anatomic breast phantom with tunable levels of radiographic tissue density for investigating contrast-enhanced detection of μcals. A phantom with tunable levels of fatty acid and albumin-agarose hydrogels was developed to mimic low-attenuating and high-attenuating fibroglandular tissues in the breast. PEGylated bisphosphonate- functionalized gold nanoparticles (BP-PEG-Au NPs) enabled contrast-enhanced detection of μcals as small as 0.5 mm in hydrogels mimicking dense breast tissue using laboratory and preclinical micro-computed tomography. Importantly BP-PEG-Au NPs also enabled contrast-enhanced detection of μcals as small as 0.1 mm in anatomic phantoms mimicking dense breast tissue using clinical mammography. Contrast enhancement decreased with increasing breast density and decreasing μcal size. The anatomic breast phantom developed in the study is expected to fill a gap in the translation of new imaging probes and methods from the laboratory to the clinic.