Differentiating malignant from benign breast lesions remains a challenge that may be met by a new imaging biomarker: lesion-to-background mechanical anisotropy assessed by VisR ultrasound. VisR is an ultrasound imaging method that uses 2 consecutive acoustic radiation force excitations, separated in time and delivered to the same region of excitation, to directionally interrogate peak displacement (PD), relative elasticity (RE), and relative viscosity (RV). From these directional measurements, mechanical degree of anisotropy is measured. In a pilot clinical study involving 29 women with BIRADS-4 or -5 breast masses, VisR PD, RE, and RV were measured in lesions and in surrounding tissue at 0°, 30°, 60°, and 90° concentric orientations. From these measurements, lesion DoA (LDoA), surrounding tissue DoA (SDoA), and log(LDoA/SDoA) were assessed per parameter and compared between biopsy-confirmed malignant versus benign masses. Across all patients, PD-, RE-, and RV-based LDoA or SDoA alone did not achieve statistical difference between malignant and benign masses (Wilcoxon, mathrm{p} > 0.05). However, PD-, RE-, and RV-based log(LDoA/SDoA) statistically differentiated malignant from benign masses (Wilcoxon, mathrm{p} < 0.01), with AUC values of 0.96 for PD-based, and 0.94 for RE- and RV-based outcomes. These results demonstrate the relevance of lesion-to-background mechanical anisotropy assessed by VisR ultrasound for differentiating malignant from benign breast masses in women, in vivo.