Objective: To compare the diagnostic performance of the automatic breast volume scanner (ABVS) against the handheld ultrasound (HHUS) in the differential diagnosis of benign and malignant breast lesions. Methods: A systematic search and review of studies involving ABVS and HHUS for breast cancer screening were performed. The search involved the data taken from Scopus, PubMed, and science direct databases and was conducted between the year 2011 to 2020. The prospective method was used in determining the inclusion and exclusion criteria while the evidence level was determined using the BI-RADS categories for diagnostic studies. In addition, the parameters of specificity, mean age, sensitivity, tumor number, and diagnostic accuracy of the ABVS and HHUS were summarized. Results: No systematic review or randomized controlled trial were identified in the systematic search while one cross-sectional study, eight retrospective studies, and 10 prospective studies were found. Sufficient follow-up of the subjects with benign and malignant findings were made only in 10 studies, in which only two had used ABVS and HHUS after performing mammographic screening and MRI. Analysis was made of 21 studies, which included 5448 lesions (4074 benign and 1374 malignant) taken from 6009 patients. The range of sensitivity was (0.72–1.0) for ABVS and (0.62–1.0) for HHUS; the specificity range was (0.52–0.98)% for ABVS and (0.49–0.99)% for HHUS. The accuracy range among the 11 studies was (80–99)% and (59–98)% for the HHUS and ABVS, respectively. The identified tumors had a mean size of 2.1 cm, and the detected cancers had a mean percentage of 94% (81–100)% in comparison to the non-cancer in all studies. Conclusions: The evidence available in the literature points to the fact that the diagnostic performance of both ABVS and HHUS are similar with reference to the differentiation of malignant and benign breast lesions.