Full-field digital mammography (FFDM), the standard of care for breast cancer screening, has some limitations. With the advent of digital breast tomosynthesis (DBT), improvements including decreased recall rates and increased cancer detection rates have been observed. The quasi-three-dimensional capability of DBT reduces breast tissue overlap, a significant limitation of FFDM. However, early studies demonstrate that a few cancers detected at FFDM may not be diagnosed at DBT-only screening, and lesions with calcifications as the dominant feature may look less suspicious at DBT or not be visible at all. These findings support the use of combined FFDM and DBT protocols to optimize screening performance. However, this combination would approximately double the patient's radiation exposure. The development of computer algorithms that generate two-dimensional synthesized mammography (SM) views from DBT has improved calcification conspicuity and sensitivity. Therefore, SM may substitute for FFDM in screening protocols, reducing radiation exposure. DBT plus SM demonstrates significantly better performance than that of FFDM alone, although there are reports of missed malignant calcifications. Thus, some centers continue to perform FFDM with DBT. Use of DBT in breast imaging has also necessitated the development of DBT-guided biopsy. DBT-guided biopsy may have a higher success rate than that of stereotactic biopsy, with a shorter procedure time. While DBT brings substantial improvements to breast cancer imaging, it is important to be aware of its strengths and limitations regarding detection of calcifications. This article reviews the imaging appearance of breast calcifications at DBT, discusses calcification biopsy techniques, and provides an overview of the current literature. Online supplemental material is available for this article. ©RSNA, 2019 An earlier incorrect version of this article appeared online. This article was corrected on February 13, 2019.