Background: The diagnosis of breast cancer is based on a clinical examination, sono-mammography, and magnetic resonance imaging. Mammography is considered a key tool in the diagnosis and early identification of breast cancer. However, a quarter of malignant cases are missed by using mammographic screening alone. Contrast-enhanced digital mammography (CEDM) has increased the opportunity for early detection and better Breast Imaging-Reporting and Data System (BI-RADS). assessment of breast cancer patients. Results: This prospective study included 115 patients, 75% were malignant and 25% were benign. Full-field digital mammography (FFDM) and CEDM were performed using the FUJIFILM Innovality mammography machine unit. The receiver operating characteristic (ROC) curve and Youden index analysis showed increased overall diagnostic performance of CEDM over FFDM alone, with the area under the curve (AUC) of 0.900 versus 0.755 (P = 0.0020). CEDM showed increased specificity 80% versus 65%, sensitivity 94.7% versus 86%, and accuracy 88.3% versus 80.5% (P <0.001) compared to FFDM alone. The calculated accuracy of CEDM in the detection of the multiplicity of malignant lesions was increased by 44.4% versus 27% compared to FFDM alone. CEDM improved the BI-RADS categorization of breast lesions and increased the accuracy in the detection of bilateral malignant breast lesions by 8.3% versus 5.5% compared to FFDM. Conclusion: CEDM is a more potent imaging modality than FFDM alone in the discrimination between benign and malignant breast lesions, it improves the accuracy of BI-RADS categorization of breast lesions and is better in the evaluation of the multiplicity of breast cancer.