Breast cancer screening with mammography is less effective in women with dense breast tissue, prompting the use of ultrasound (US) imaging. While two- (2D) and three-dimensional (3D) US improve cancer detection, their low specificity leads to frequent unnecessary biopsies. Operator dependence on 2D US has led to the development of 3D automated breast volume scanners (ABVS), but challenges remain in distinguishing benign from malignant lesions. We developed a 3D photoacoustic and ultrasound (PAUS)–ABVS system that integrates a large field-of-view, 768-element transducer to improve diagnostic accuracy. In a clinical study of 61 patients with 36 benign and 30 malignant lesions, multispectral photoacoustic imaging was used to measure blood volume and oxygen saturation within lesions. When combined with standard US BI-RADS (breast imaging reporting and data system) scores, the system achieved a sensitivity of 96.7% and specificity of 66.7%. This performance matched the best outcomes of 2D PAUS and outperformed conventional US. Our results suggest that the PAUS-ABVS can support more accurate breast cancer diagnosis while reducing unnecessary biopsies.