Digital breast tomosynthesis (DBT) is a novel modality with the potential to improve early detection of breast cancer by providing three-dimensional (3D) imaging with a low radiation dose. 3D image reconstruction presents some challenges: cone-beam and flat-panel geometry, and highly incomplete sampling. A promising means to overcome these challenges is statistical iterative reconstruction (IR), since it provides the flexibility of accurate physics modeling and a general description of system geometry. The authors’ goal was to develop techniques for applying statistical IR to tomosynthesis imaging data