To compare diffusion-kurtosis imaging (DKI) and diffusion-weighted imaging (DWI) parameters of single-shot echo-planar imaging (ss-EPI) and readout-segmented echo-planar imaging (rs-EPI) in the differentiation of luminal vs. non-luminal breast cancer using histogram analysis. One hundred and sixty women with 111 luminal and 49 non-luminal breast lesions were enrolled in this study. All patients underwent ss-EPI and rs-EPI sequences on a 3.0T scanner. Histogram metrics were derived from mean kurtosis (MK), mean diffusion (MD) and the apparent diffusion coefficient (ADC) maps of two DWI sequences respectively. Student's t test or Mann-Whitney U test was performed for differentiating luminal subtype from non-luminal subtype. The ROC curves were plotted for evaluating the diagnostic performances of significant histogram metrics in differentiating luminal from non-luminal BC. The histogram metrics MKmean, MK50th, MK75th of luminal BC were significantly higher than those of non-luminal BC for both two DWI sequences (all P<0.05). Histogram metrics from rs-EPI sequence had better diagnostic performance in differentiating luminal from non-Luminal breast cancer compared to those from ss-EPI sequence. MK75th derived from rs-EPI sequence was the most valuable single metric (AUC, 0.891; sensitivity, 78.4%; specificity, 87.8%) for differentiating luminal from non-luminal BC among all the histogram metrics. Histogram metrics of MK derived from rs-EPI yielded better diagnostic performance for distinguishing luminal from non-luminal BC than that from ss-EPI. MK75th was the most valuable metric among all the histogram metrics.© 2024. The Author(s).