Contrast-enhanced mammography (CEM) is a relatively new imaging technique that allows morphologic, anatomic and functional imaging of the breast. The aim of our study was to validate contrast-enhanced mammography (CEM) compared to mammography (MMG) and digital breast tomosynthesis (DBT) in daily clinical practice. This retrospective study included 316 consecutive patients who underwent MMG, DBT and CEM at the Centre for Prevention and Diagnosis of Chronic Diseases of Primorsko-goranska County. Two breast radiologists independently analyzed the image data, without available anamnestic information and without the possibility of comparison with previous images, to determine the presence of suspicious lesions and their morphological features according to the established criteria of the Breast Imaging Reporting and Data System (BI-RADS) lexicon. The diagnostic value of MMG, DBT and CEM was assessed by ROC analysis. The interobserver agreement was excellent. CEM showed higher diagnostic accuracy in terms of sensitivity and specificity compared to MMG and DBT, the reporting time for CEM was significantly shorter, and CEM findings resulted in a significantly lower proportion of equivocal findings (BI-RADS 0), suggesting fewer additional procedures. In conclusion, CEM achieves high diagnostic accuracy while maintaining simplicity, reproducibility and applicability in complex clinical settings.