PurposeTo investigate the application of whole-lesion histogram analysis of pharmacokinetic parameters for differentiating malignant from benign breast lesions on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Materials and MethodsIn all, 92 women with 97 breast lesions (26 benign and 71 malignant lesions) were enrolled in this study. Patients underwent dynamic breast MRI at 3T using a prototypical CAIPIRINHA-Dixon-TWIST-VIBE (CDT-VIBE) sequence and a subsequent surgery or biopsy. Inflow rate of the agent between plasma and interstitium (K-trans), outflow rate of agent between interstitium and plasma (K-ep), extravascular space volume per unit volume of tissue (v(e)) including mean value, 25th/50th/75th/90th percentiles, skewness, and kurtosis were then calculated based on the whole lesion. A single-sample Kolmogorov-Smirnov test, paired t-test, and receiver operating characteristic curve (ROC) analysis were used for statistical analysis. ResultsMalignant breast lesions had significantly higher K-trans, K-ep, and lower v(e) in mean values, 25th/50th/75th/90th percentiles, and significantly higher skewness of v(e) than benign breast lesions (all P < 0.05). There was no significant difference in kurtosis values between malignant and benign breast lesions (all P > 0.05). The 90th percentile of K-trans, the 90th percentile of K-ep, and the 50th percentile of v(e) showed the greatest areas under the ROC curve (AUC) for each pharmacokinetic parameter derived from DCE-MRI. The 90th percentile of K-ep achieved the highest AUC value (0.927) among all histogram-derived values. ConclusionThe whole-lesion histogram analysis of pharmacokinetic parameters can improve the diagnostic accuracy of breast DCE-MRI with the CDT-VIBE technique. The 90th percentile of K-ep may be the best indicator in differentiation between malignant and benign breast lesions. Level of Evidence: 4 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2018;47:91-96.