Background: Histogram analysis of the diffusion-weighted imaging (DWI) parameters is widely used to differentiate the breast lesions. However, histogram analysis of the diffusion-kurtosis imaging ( DKI) parameters for the single-shot echo-planar imaging (ss-EPI) and readout- segmented echo planar imaging (rs-EPI) sequences has not been compared in breast cancer. Thus, this study is to investigate the diagnostic accuracy and reliability of the histogram parameters derived from the rs-EPI and ss-EPI sequences of DKI parameters in distinguishing between the benign and malignant breast lesions. Methods: This single-center, retrospective cohort study enrolled 205 consecutive patients with breast lesions (65 benign and 140 malignant). The patients underwent breast magnetic resonance imaging (MRI) with a 3T scanner using the rs-EPI and ss-EPI sequences with 4 b values (0, 50, 1,000, and 2,000 s/mm(2)). The regions of interest (ROIs) were manually delineated for all the lesion images from both the sequences, and the histogram parameters were extracted from the apparent diffusion coefficient (ADC) and apparent diffusional kurtosis (K-app) maps. Statistical analysis was performed using the Kolmogorov-Smirnov test, the student's t-test, and the receiver operating characteristic (ROC) curves. Results: The mean, 25th, 50th, 75th, and 100th percentiles, skewness, and kurtosis values derived from apparent diffusion for non- Gaussian distribution (D-app) and K-app maps showed good or excellent intraobserver agreement (ICC: 0.695 to 0.863).The mean and the 25th, 50th, 75th, and 100th percentile values for Dapp were significantly lower and the mean and the 25th, 50th, 75th, and 100th percentile values for K-app were significantly higher in the malignant breast lesions compared with those in the benign breast lesions for both the rs-EPI and ss-EPI sequences (all P<0.05). The majority of the histogram K-app and D-app parameters (except skewness and kurtosis) for the benign and malignant lesions showed significant differences between the ss-EPI and the rs-EPI sequences (P<0.05). ROC curve analysis showed that the AUC values for the 75th percentile of K-app (0.854 for rs-EPI, 0.844 for ss-EPI) and the 25th percentile of D-app (0.866 for rs-EPI, 0.858 for ss-EPI) were highest for both DKI sequences. The diagnostic performance of the rs-EPI sequence was better than the ss-EPI sequence for all the histogram parameters except the skewness value of D-app. Conclusions: Histogram parameters from the rs-EPI sequence were more reliable and accurate in differentiating malignant and benign breast lesions than those from the ss-EPI sequence.