To determine whether there are differences in the biopsy outcomes for suspicious calcifications detected with screening mammography using the digital breast tomosynthesis and synthetic 2D (DBT/SM) technique compared to calcifications detected using the full-field digital (DM) technique. This retrospective study was IRB approved. The records for all stereotactic biopsies performed for suspicious calcifications detected on screening mammograms using DM in 2011-2014 and DBT/SM in 2017-2020 were reviewed. We collected patient, imaging, and pathology data from the breast imaging database and from retrospective review of a subset of mammograms. The biopsy outcome results were categorized as benign, benign with upgrade potential (BWUP), and malignant based on final pathology. Frequencies and proportions of outcomes were calculated and compared using Mann-Whitney U tests and Wilcoxson signed-rank tests with P-values and 95% confidence intervals (95% CIs). From 2011 to 2014 (DM), 1274 stereotactic biopsies of calcifications yielded 74.2% (945/1274) benign, 11.5% (147/1274) BWUP, and 14.3% (182/1274) malignant outcomes. From 2017 to 2020 (DBT/SM), 1049 stereotactic biopsies yielded 65.2% (684/1049) benign, 15.6% (164/1049) BWUP, and 19.2% (201/1049) malignant outcomes. With DBT/SM, benign biopsy outcomes decreased (9.0%, 95% CI 0.87-11.53, P < 0.05), whereas malignant biopsy outcomes increased (4.9%, 95% CI 0.94-8.36, P < 0.05). There was no significant difference in BWUP biopsy outcomes and total biopsy rates between techniques (P > 0.05). Calcifications detected with screening DBT/SM technique were significantly more likely to be malignant than those found using DM. These results support using the DBT/SM technique without obtaining concurrent DM images.