Background <p>Preoperative diagnosis of multifocal and multicentric breast cancer (MMBC) is crucial for surgical planning either for mastectomy or performing conservative management. Contrast-enhanced spectral mammography (CESM) is more applicable compared to MRI, yet it shows lower sensitivity in the evaluation of disease extension.</p> Aim of the work <p>To compare the diagnostic accuracy of CESM in the detection of additional suspicious lesions in patients with breast cancer and the diagnosis of the MMBC compared to contrast-enhanced magnetic resonance imaging (CE-MRI).</p> Results <p>This retrospective study was performed during the period between January 2020 and January 2024 including 60 patients diagnosed as breast cancer with suspected multifocality or multicentricity, and they all underwent both CESM and breast contrast-enhanced MRI for preoperative staging. CESM sensitivity, specificity and diagnostic accuracy for the diagnosis of additional lesions were estimated and compared to CE-MRI with significance which was considered (<i>p</i> value &lt; 0.05). The postoperative pathological results were considered as the gold standard test.</p> <p>Our study showed comparable sensitivity of CESM (97%), and slightly higher diagnostic accuracy (95%) compared to CE-MRI (sensitivity = 99% and diagnostic accuracy = 94%) with no significant differences and with significantly higher specificity (CESE = 67%&amp; CE- MRI = 33%) making CESM another promising method of MMBC breast diagnosis providing similar dedicated morphological and functional description about the lesion.</p> Conclusions <p>CESM is a valuable imaging modality for evaluation and diagnosis of MMBC with comparable sensitivity and accuracy and higher specificity compared to MRI so it can be considered as a promising alternative technique to CE-MRI.</p>