Background: Digital breast tomosynthesis (DBT) is a new imaging modality for improving breast cancer detection because it allowed for better detection of abnormalities, especially in females with dense breasts, and the diagnosis of benign lesions, which resulted in fewer recalled cases and negative biopsies, as well as assessing therapeutic efficacy. Objectives: Evaluation of the diagnostic validity of 3D wide-angle Digital Breast Tomosynthesis (WA-DBT) during screening programs for breast cancer (BC). Patients and Methods: 449 women with breast lesions who attended the screening campaign were examined by Full-field Digital Mammography (DMG) and WA-DBT using Hologic™ Selenia® Dimensions® 3D Performance System and ultrasound (US) imaging using GE LOGIQ P7® linear probe (7-12 MHz). Then, a surgical biopsy was obtained from women who had lesions of BI-RADS grade 4 or 5 and examined pathologically, the pathological diagnosis was used as the gold standard for comparison of radiological diagnoses. Results: Pathological diagnosis defined30 malignant and 9 benign lesions. The performance characteristics of WA-DBT imaging were superior to that of DMG and US and the agreement of diagnoses obtained by WA-DBT and both DMG and US was moderate and substantial with κ coefficient of 0.421 and 0.726, respectively. ROC curve analysis defined WA-DBT as the best diagnostic test with a significantly higher area under the curve (AUC) in relation to the reference AUC as a discriminative diagnostic modality for breast lumps of BI-RADS grade 5 and as the most sensitive modality for differentiation between masses that are probably benign (BI-RADS grade 3) and that suspicious of malignancy (BI-RADS grade 4). Conclusion: WA-DBT is a valuable radiologic modality for screening women with breast lesions especially those in dense/extremely dense breasts. Also, WA-DBT can precisely identify microcalcifications obscuring very small-to-small breast lesions thus allowing early detection of BC.