We investigated the clinical impact of breast scintigraphy acquired with a breast specific γ-camera (BSGC) in the diagnosis of breast cancer (BC) and assessed its incremental value over mammography (Mx). A consecutive series of 467 patients underwent BSGC scintigraphy for different indications: suspicious lesions on physical examination and/or on US/MRI negative at Mx (BI-RADS 1 or 3), characterization of lesions suspicious at Mx (BI-RADS 4), preoperative staging in lesions highly suggestive of malignancy at Mx (BI-RADS 5). Definitive histopathological findings were obtained in all cases after scintigraphy: 420/467 patients had BC, while 47/467 patients had benign lesions. The scintigraphic data were correlated to Mx BI-RADS category findings and to histology. The incremental value of scintigraphy over Mx was calculated. Scintigraphy was true-positive in 97.1% BC patients, detecting 96.2% of overall tumor foci, including 91.5% of carcinomas ≤10 mm, and it was true-negative in 85.1% of patients with benign lesions. Scintigraphy gave an additional value over Mx in 141/467 cases (30.2%). In particular, scintigraphy ascertained BC missed at Mx in 31 patients with BI-RADS 1 or 3, including 26 patients with heterogeneously/high dense breast (19/26 with tumors ≤10 mm) and detected additional clinically occult ipsilateral or controlateral tumor foci (all <10 mm) or the in situ component sited around invasive tumors in 77 BC patients with BI-RADS 4 or 5, changing surgical management in 18.2% of these cases; moreover, scintigraphy ruled out malignancy in 33 patients with BI-RADS 4. BSGC scintigraphy proved a highly sensitive diagnostic tool, even in small size carcinoma detection, while maintaining a high specificity. The procedure increased both the sensitivity of Mx, especially in dense breast and in multifocal/multicentric disease, and the specificity as well as it better defined local tumor extension, thus guiding the surgeon to a more appropriate surgical treatment.