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Breast conservative surgery is the primary therapeutic choice for non-aggressive early breast cancers, and a minimally-invasive approach is strongly recommended. The breast localization represents a modern challenge for surgery. Wire-guided localization is still the gold standard technique, but new wireless systems have been proposed, such as radiofrequency identification with LOCalizerTM (Hologic, Santa Carla, CA, USA), which reports encouraging results. The current study aimed to evaluate the accuracy and efficacy of the combined use of LOCalizerTM and ultrasound compared with the results obtained using LOCalizerTM alone for the detection of non-palpable breast cancer. Ninety-six patients who were candidates for breast localization were enrolled. Group A received a combined localization with LOCalizerTM and US, while group B underwent only LOCalizerTM identification. Oncological radicality was reached in 100% of the patients in Group A and in 89.2% of the patients in Group B, with p = 0.006. The mean specimens’ volume was 13.2 ± 0.6 cm3 for Group A and 16.1 ± 1.4 cm3 for Group B, while mean specimen weights were 21.8 ± 2.2 and 24.4 ± 1.8 g, respectively (p = 0.003 and p = 0.004, respectively). LOCalizerTM with ultrasound, in the current series, has resulted in the preferred option for the localization of non-palpable breast cancer, allowing limited resection (in weight and volume), guaranteeing excellent oncological outcomes, and great satisfaction for patients and physicians.