The purpose of this study was to assess the accuracy of stereotactic vacuum-assisted biopsy (SVAB) for the diagnosis of high-risk lesions, which include papillary lesions and atypical lobular hyperplasia (ALH). Retrospective review was performed of 212 consecutive SVABs at our institution between May 1, 2000 and February 28, 2001. Biopsies were performed using an 8-gauge SVAB probe, with the patient prone on a dedicated stereotactic table. Eleven to 17 cores (mean 12.4) were harvested from each lesion. Radiography of core specimens was performed in cases in which the targeted lesion contained microcalcifications. Six of the lesions (2.8%) demonstrated intraductal papilloma, 1 (16.7%) of which had features suggestive of a radial scar, and 7 (3.3%) demonstrated ALH. Surgical excision was performed on 3 of the 6 (50%) papillomas and all 7 (100%) cases of ALH. Histopathologic analysis at surgical excision demonstrated benign breast tissue in 1 of the papillomas (33.3%), radial scar in 1 (33.3%), and atypical ductal hyperplasia (ADH) in 1 (33.3%). One papilloma not surgically excised underwent repeat mammography at 6 months and demonstrated no change. Of the surgically excised lesions with ALH, 4 (57.1%) retained the diagnosis of ALH, though one of these (25%) also demonstrated a coexisting radial scar. One lesion (14.3%) demonstrated ductal carcinoma in situ (DCIS), 1 (14.3%) demonstrated lobular carcinoma in situ (LCIS), and 1 (14.3%) demonstrated fibrocystic change. Lesions diagnosed as papillomas at SVAB did not demonstrate malignancy, but 2 (66.7%) were found to contain high-risk lesions that may impact surveillance or prophylactic therapy (i.e., tamoxifen). Because of the relatively small series reported, additional studies are necessary to further assess the accuracy of SVAB in the diagnosis of benign papillary lesions. ALH diagnosed with SVAB that underwent subsequent surgical excision demonstrated cancer in 1 of 7 lesions (14.3%). This rate of cancer underestimation is similar to that seen with ADH diagnosed with SVAB, which warrants surgical excision to rule out malignancy. Therefore we recommend that lesions demonstrating ALH at SVAB be considered for surgical excision to rule out malignancy.