The aim of this study was to evaluate if re-biopsy with 10-gauge vacuum-assisted biopsy (VAB) could get definitive diagnosis for breast lesions with ultrasound (US) imaging-histologic discordance at 16-gauge core needle biopsy (CNB). From January 2007 to June 2008, a consecutive biopsy was performed on 1069 lesions with US-guided 16-gauge CNB. A total of 28 lesions were considered to be US imaging-histologic discordant and all of them underwent subsequent 10-gauge VAB. All malignant lesions located at VAB were treated with subsequent surgery and all benign lesions at VAB were followed up for at least 1 year. Six of the 28 lesions (21.4%) had pathologic upgrade after VAB. In them, one case upgraded from adenosis to ductal carcinoma in situ (DCIS); one case upgraded from adenosis to infiltrating ductal carcinoma (IDC); one case upgraded from atypical ductal hyperplasia to IDC; two cases upgraded from intraductal papilloma to DCIS; and one case upgraded from sclerosing adenosis to invasive lobular carcinoma (ILC). The subsequent surgery further demonstrated the diagnosis of VAB for all the lesions with histologic upgrade. Re-biopsy could improve diagnostic accuracy in patients with breast lesions showing imaging-histologic discordance during CNB, and 10-gauge VAB was a valuable method to deal with re-biopsy.