Purpose: To quantitatively evaluate a superresolution technique for 3D, one-millimeter isotropic diffusion-weighted imaging (DWI) of the whole breasts. Methods: Isotropic 3D DWI datasets are obtained using a combination of (i) a readout-segmented diffusion-weighted-echo-planar imaging (DW-EPI) sequence (rs-EPI), providing high in-plane resolution, and (ii) a superresolution (SR) strategy, which consists of acquiring 3 datasets with thick slices (3 mm) and 1-mm shifts in the slice direction, and combining them into a 1 × 1 × 1-mm3 dataset using a dedicated reconstruction. Two SR reconstruction schemes were investigated, based on different regularization schemes: conventional Tikhonov or Beltrami (an edge-preserving constraint). The proposed SR strategy was compared to native 1 × 1 × 1-mm3 acquisitions (i.e. with 1-mm slice thickness) in 8 healthy subjects, in terms of signal-to-noise ratio (SNR) efficiency, using a theoretical framework, Monte Carlo simulations and region-of-interest (ROI) measurements, and image sharpness metrics. Apparent diffusion coefficient (ADC) values in normal breast tissue were also compared. Results: The SR images resulted in an SNR gain above 3 compared to native 1 × 1 × 1-mm3 using the same acquisition duration (acquisition gain 3 and reconstruction gain >1). Beltrami-SR provided the best results in terms of SNR and image sharpness. The ADC values in normal breast measured from Beltrami-SR were preserved compared to low-resolution images (1.91 versus 1.97 ×10-3 mm2 /s, P = .1). Conclusion: A combination of rs-EPI and SR allows 3D, 1-mm isotropic breast DWI data to be obtained with better SNR than a native 1-mm isotropic acquisition. The proposed DWI protocol might be of interest for breast cancer monitoring/screening without injection.