To investigate possible associations between quantitative apparent diffusion coefficient (ADC) metrics derived from whole-lesion histogram analysis and breast cancer recurrence risk in women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-negative breast cancer who underwent the Oncotype DX assay. This retrospective study was conducted on 105 women (median age, 48 years) with ER-positive, HER2-negative, node-negative breast cancer who underwent the Oncotype DX test and preoperative diffusion-weighted imaging (DWI). Histogram analysis of pixel-based ADC data of whole tumors was performed, and various ADC histogram parameters (mean, 5th, 25th, 50th, 75th, and 95th percentiles of ADCs) were extracted. The ADC difference value (defined as the difference between the 5th and 95th percentiles of ADCs) was calculated to assess intratumoral heterogeneity. Associations between quantitative ADC metrics and the recurrence risk, stratified using the Oncotype DX recurrence score (RS), were evaluated. Whole-lesion histogram analysis showed that the ADC difference value was different between the low-risk recurrence (RS < 18) and the non-low-risk recurrence (RS ≥ 18; intermediate to high risk of recurrence) groups (0.600 × 10-3 mm2/s vs. 0.746 × 10-3 mm2/s, p < 0.001). Multivariate regression analysis demonstrated that a lower ADC difference value (< 0.559 × 10-3 mm2/s; odds ratio [OR] = 5.998; p = 0.007) and a small tumor size (≤ 2 cm; OR = 3.866; p = 0.012) were associated with a low risk of recurrence after adjusting for clinicopathological factors. The ADC difference value derived from whole-lesion histogram analysis might serve as a quantitative DWI biomarker of the recurrence risk in women with ER-positive, HER2-negative, node-negative invasive breast cancer. • A lower ADC difference value and a small tumor size were associated with a low risk of recurrence of breast cancer. • The ADC difference value could be a quantitative marker for intratumoral heterogeneity. • Whole-lesion histogram analysis of the ADC could be helpful for discriminating the low-risk from non-low-risk recurrence groups.