To compare the performance of one-view digital breast tomosynthesis (1v-DBT) to that of three other protocols combining DBT and mammography (DM) for breast cancer detection. Six radiologists, three experienced with 1v-DBT in screening, retrospectively reviewed 181 cases (76 malignant, 50 benign, 55 normal) in two sessions. First, they scored sequentially: 1v-DBT (medio-lateral oblique, MLO), 1v-DBT (MLO) + 1v-DM (cranio-caudal, CC) and two-view DM + DBT (2v-DM+2v-DBT). The second session involved only 2v-DM. Lesions were scored using BI-RADS® and level of suspiciousness (1-10). Sensitivity, specificity, receiver operating characteristic (ROC) and jack-knife alternative free-response ROC (JAFROC) were computed. On average, 1v-DBT was non-inferior to any of the other protocols in terms of JAFROC figure-of-merit, area under ROC curve, sensitivity or specificity (p>0.391). While readers inexperienced with 1v-DBT screening improved their sensitivity when adding more images (69-79 %, p=0.019), experienced readers showed similar sensitivity (76 %) and specificity (70 %) between 1v-DBT and 2v-DM+2v-DBT (p=0.482). Subanalysis by lesion type and breast density showed no difference among modalities. Detection performance with 1v-DBT is not statistically inferior to 2v-DM or to 2v-DM+2v-DBT; its use as a stand-alone modality might be sufficient for readers experienced with this protocol. • One-view breast tomosynthesis is not inferior to two-view digital mammography. • One-view DBT is not inferior to 2-view DM plus 2-view DBT. • Training may lead to 1v-DBT being sufficient for screening.