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Background: Ultrasound plays a crucial role in early diagnosis of breast cancer. The aim of this research is to evaluate the diagnostic performance of BI-RADS classification in comparison with new semi-automatic software Resona R9, Mindray, “SmartBreast” and strain elastography (SE), point shear wave (pSWE), and 2D shear wave (2D SWE) Elastography for breast lesion differentiation. Methods: Ninety-two breast nodules classified according to BI-RADS lexicon by an expert radiologist were evaluated by a second investigator with B-mode ultrasound, color Doppler, “SmartBreast”, and elastography. Histopathology was considered the gold standard. Results: The agreement between software and investigator was excellent in the identification of the posterior features of breast masses (Cohen’s k = 0.94), good for shape and vascular signal (Cohen’s k, respectively, of 0.6 and 0.65), poor for orientation, margins, and echo pattern (Cohen’s k, respectively, of 0.28, 0.33 and 0.48), moderate for dimensions (Lin’s correlation coefficient of 0.90, p = 0.07). SE showed a greater area under curve (AUC) than pSWE and 2D SWE (0.84, 0.64, and 0.61, respectively), with a greater specificity and a comparable sensitivity to pSWE (respectively, of 0.86 and 0.55, 0.81 and 0.84). Conclusions: SE improved the diagnostic performance of BI-RADS classification more than pSWE and 2D SWE; “SmartBreast” showed good agreement only for shape and vascularization but not for the other ultrasound features of breast lesions.