Background: Equivocal and indeterminate breast lesions which are detected on sonomammography should be further evaluated by either biopsy or follow-up. Contrast-enhanced digital mammography can act as a problem-solving tool to avoid biopsies of some problematic breast lesions and help clinicians to take a proper decision about these lesions in the same setting. Objective: This study aimed to evaluate the complementary role of contrast-enhanced digital mammography (CEDM) to characterize indeterminate and equivocal breast lesions detected on sonomammography and its role to downgrade or upgrade the final BI-RADS category of these lesions. Patients and Methods: This prospective study included 35 females with mean age of 48.26 years. Ladies were referred from the clinic for screening mammograms during the period from august 2020 to September 2021. Results: Contrast-enhanced digital mammography showed higher specificity (86.4%), PPV (80.0%), NPV (95.0%), and accuracy (88.6%). While sonomammography revealed specificity of 63.6%, PPV of 60.0%, NPV of 93.3%, and accuracy of 74.29%. However, both showed a comparable sensitivity of about 92.3%. Fourteen lesions (40%) were downgraded by CEDM and proved to be benign lesions and five lesions (14.2%) were upgraded and proved to be malignant lesions. Conclusion: Contrast-enhanced digital mammography is a promising technique in the characterization of equivocal and indeterminate breast lesions (BI-RADS 3 and 4). It can be utilized to help in the final assessment of these findings in the same setting and offer assistance in avoiding biopsies in numerous patients with more prominent specificity and precision than sonomammography.