The purpose of this study was to compare contrast-enhanced spectral mammography (CESM) with mammography (MG) and combined CESM + MG in terms of detection and size estimation of histologically proven breast cancers in order to assess the potential to reduce radiation exposure. A total of 118 patients underwent MG and CESM and had final histological results. CESM was performed as a bilateral examination starting 2 min after injection of iodinated contrast medium. Three independent blinded radiologists read the CESM, MG, and CESM + MG images with an interval of at least 4 weeks to avoid case memorization. Sensitivity and size measurement correlation and differences were calculated, average glandular dose (AGD) levels were compared, and breast densities were reported. Fisher's exact and Wilcoxon tests were performed. A total of 107 imaging pairs were available for analysis. Densities were ACR1: 2, ACR2: 45, ACR3: 42, and ACR4: 18. Mean AGD was 1.89 mGy for CESM alone, 1.78 mGy for MG, and 3.67 mGy for the combination. In very dense breasts, AGD of CESM was significantly lower than MG. Sensitivity across readers was 77.9 % for MG alone, 94.7 % for CESM, and 95 % for CESM + MG. Average tumor size measurement error compared to postsurgical pathology was -0.6 mm for MG, +0.6 mm for CESM, and +4.5 mm for CESM + MG (p < 0.001 for CESM + MG vs. both modalities). CESM alone has the same sensitivity and better size assessment as CESM + MG and was significantly better than MG with only 6.2 % increase in AGD. The combination of CESM + MG led to systematic size overestimation. When a CESM examination is planned, additional MG can be avoided, with the possibility of saving up to 61 % of radiation dose, especially in patients with dense breasts.