The Kaiser score (KS) is a simple and intuitive machine-learning derived decision rule for characterizing breast lesions in a clinical setting and screening for breast cancer. The present study aims to investigate the applicability of the KS for contrast-enhanced mammography (CEM) in breast masses, and to compare its diagnostic accuracy with magnetic resonance imaging (MRI). CEM may provide an alternative option for patients with breast masses, especially for those with MRI contraindications.Two hundred and seventy-five patients with breast enhanced masses were included in the study from May 2019 to September 2022. Patients were further divided into benign and malignant groups based on pathological diagnosis. The CEM and MRI imaging characteristics of these two groups were analyzed statistically. The paired chi-square and Cohen's kappa coefficient (κ) analysis were used to compare imaging characteristics between CEM and MRI. The Breast Imaging Reporting and Data System (BI-RADS) and KS for CEM and MRI were evaluated based on imaging characteristics. The diagnostic performance of BI-RADS and KS for CEM and MRI was assessed and compared using receiver operating characteristic (ROC) analysis and DeLong's test.The imaging characteristics of root sign, time-signal intensity curve (TIC/mTIC), margin, internal enhancement pattern (IEP), edema, apparent diffusion coefficient (ADC) values, and suspicious malignant microcalcifications showed significant differences between benign and malignant lesions (all p ≤ 0.011). The detection rate of root sign and margin showed substantial agreement between CEM and MRI (κ = 0.656, κ = 0.640), but IEP, TIC/mTIC, and edema showed poor agreement (κ = 0.380, κ = 0.320, κ = 0.324). For all lesion analyses, the area under the curves (AUCs) of the KS (0.897 ∼ 0.932) were higher than that of BI-RADS (0.691) in CEM (all p < 0.001). The AUC of KS (calcification)-CEM (0.932) was higher than those of both KS-CEM and KS (edema)-CEM (0.897 and 0.899) (all p < 0.001). For subgroup analyses, the AUCs of the KS (0.875 ∼ 0.876) were higher than that of BI-RADS (0.740) in MRI (all p < 0.001). The AUCs of KS-MRI (0.876) and KS (ADC)-MRI (0.875) were similar to those of KS-CEM (0.878) and KS (edema)-CEM (0.870) (all p > 0.100). The AUC of KS (calcification)-CEM (0.934) was slightly higher than those of both KS-MRI (0.876) and KS (ADC)-MRI (0.875), but no significant difference was observed (p = 0.051; p = 0.071).The KS for CEM provided high diagnostic accuracy in distinguishing breast masses, comparable to that of MRI. The application of KS (calcification)-CEM combined with suspicious malignant microcalcifications can improve diagnostic efficiency with an AUC of 0.932 ∼ 0.934. However, edema did not significantly improve performance when using the KS for CEM.Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.