Objective: Our aim was to compare the ability of radiologists to detect breast cancers using one-view breast tomosynthesis (BT) and two-view digital mammography (DM) in an enriched population of abnormal (diseased) patients and benign and/or normal (healthy) patients. Methods: All participants gave informed consent. The BT and DM examinations were performed with about the same average glandular dose to the breast. The study population comprised patients with subtle signs of malignancy seen on DM and/or ultrasonography. Ground truth was established by pathology, needle biopsy and/or by 1-year follow-up by mammography, which retrospectively resulted in 89 abnormal breasts (one breast per patient) with 95 malignant lesions and 96 normal or benign breasts. Two experienced radiologists, non-participants in the study, determined the locations of the malignant lesions. Five radiologists, experienced in mammography, interpreted the cases independently in a free-response study. The data were analysed by the receiver operating characteristic (ROC) and jackknife alternative free-response ROC (JAFROC) methods, regarding both readers and cases as random effects. Results: The diagnostic accuracy of BT was significantly better than that of DM (JAFROC: p = 0.0031, ROC: p = 0.0415). The average sensitivity of BT was higher than that for DM (∼90 vs ∼79%; 95% confidence interval of difference: 0.036, 0.108) while the average false positive fraction was not significantly different (95% confidence interval of difference: -0.117, 0.010).Conclusion: The diagnostic accuracy of BT was superior to DM in an enriched population.