Analysis of complex imaging tasks requires a phantom that simulates the patient anatomy. We have developed a technique to fabricate 3D physical anthropomorphic breast phantoms for image quality assessment of 2D and 3D breast x-ray imaging systems. The phantom design is based on an existing computer model that can generate breast voxel phantoms of varying size, shape, glandularity, and internal composition. The physical phantom is produced in two steps. First, the computer model of the glandular tissue, skin and Coopers' ligaments is separated into sections. These sections are fabricated by high-resolution rapid prototype printing using a single tissue equivalent material. The adipose tissue regions in the sections are filled using an epoxy-based resin combined with phenolic microspheres. The phantom sections are then stacked. The phantom is provided with an extra section modified to include iodine-enhanced masses. We fabricated a prototype phantom corresponding to a 450 ml breast with 45% dense tissue deformed to represent a 5 cm compressed thickness. The rapid prototype and epoxy based resin phantom materials attenuate x rays similar to 50% glandular tissue and 100% adipose tissue, respectively. The iodinated masses are between 4.0 and 9.6 mm thick and contain 2.5 mg/ml and 5 mg/ml iodine. Digital mammography and digital breast tomosynthesis images of the phantom are qualitatively similar in appearance to clinical images. In summary, a method to fabricate a 3D physical anthropomorphic breast phantom has been developed with known ground truth in the form of a companion voxel phantom. This combined system of physical and computational phantoms allows for both qualitative and quantitative image quality assessment.© (2010) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.