BackgroundMRI‐based radiomics has been used to diagnose breast lesions; however, little research combining quantitative pharmacokinetic parameters of dynamic contrast‐enhanced MRI (DCE‐MRI) and diffusion kurtosis imaging (DKI) exists.PurposeTo develop and validate a multimodal MRI‐based radiomics model for the differential diagnosis of benign and malignant breast lesions and analyze the discriminative abilities of different MR sequences.Study TypeRetrospective.PopulationIn all, 207 female patients with 207 histopathology‐confirmed breast lesions (95 benign and 112 malignant) were included in the study. Then 159 patients were assigned to the training group, and 48 patients comprised the validation group.Field Strength/SequenceT2‐weighted (T2W), T1‐weighted (T1W), diffusion‐weighted MR imaging (b‐values = 0, 500, 800, and 2000 seconds/mm2) and quantitative DCE‐MRI were performed on a 3.0T MR scanner.AssessmentRadiomics features were extracted from T2WI, T1WI, DKI, apparent diffusion coefficient (ADC) maps, and DCE pharmacokinetic parameter maps in the training set. Models based on each sequence or combinations of sequences were built using a support vector machine (SVM) classifier and used to differentiate benign and malignant breast lesions in the validation set.Statistical TestsOptimal feature selection was performed by Spearman's rank correlation coefficients and the least absolute shrinkage and selection operator algorithm (LASSO). Receiver operating characteristic (ROC) curves were used to assess the diagnostic performance of the radiomics models in the validation set.ResultsThe area under the ROC curve (AUC) of the optimal radiomics model, including T2WI, DKI, and quantitative DCE‐MRI parameter maps was 0.921, with an accuracy of 0.833. The AUCs of the models based on T1WI, T2WI, ADC map, DKI, and DCE pharmacokinetic parameter maps were 0.730, 0.791, 0.770, 0.788, and 0.836, respectively.Data ConclusionThe model based on radiomics features from T2WI, DKI, and quantitative DCE pharmacokinetic parameter maps has a high discriminatory ability for benign and malignant breast lesions.Level of Evidence3Technical Efficacy Stage2 J. Magn. Reson. Imaging 2020;52:596–607.