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Rationale and Objectives: Optimization studies for x-ray-based breast imaging systems using computer simulation can greatly benefit from a phantom capable of modeling varying anatomical variability across different patients. This study aimed to develop a three-dimensional phantom model with realistic and randomizable anatomical features., Materials and Methods: A voxelized breast model was developed consisting of an outer layer of skin and subcutaneous fat, a mixture of glandular and adipose, stochastically generated ductal trees, masses, and microcalcifications. Randomized realization of the breast morphology provided a range of patient models. Compression models were included to represent the breast under various compression levels along different orientations. A Monte Carlo (MC) simulation code was adapted to simulate x-ray based imaging systems for the breast phantom. Simulated projections of the phantom at different angles were generated and reconstructed with iterative methods, simulating mammography, breast tomosynthesis, and computed tomography (CT) systems. Phantom dose maps were further generated for dosimetric evaluation., Results: Region of interest comparisons of simulated and real mammograms showed strong similarities in terms of appearance and features. Noise-power spectra of simulated mammographic images demonstrated that the phantom provided target properties for anatomical backgrounds. Reconstructed tomosynthesis and CT images and dose maps provided corresponding data from a single breast enabling optimization studies. Dosimetry result provided insight into the dose distribution difference between modalities and compression levels., Conclusion: The anthropomorphic breast phantom, combined with the MC simulation platform, generated a realistic model for a breast imaging system. The developed platform is expected to provide a versatile and powerful framework for optimizing volumetric breast imaging systems., (Copyright © 2011 AUR. Published by Elsevier Inc. All rights reserved.)