Five hundred ultrasonographically guided large-core needle breast biopsies of solid masses were performed in 446 women. Histopathologic results were correlated with imaging findings. Ultrasonographically guided large-core needle biopsy resulted in diagnosis of malignancy (n = 124) or severe atypical ductal hyperplasia (n = 4) in 128 lesions (26%). In the remaining 372 lesions (74%), ultrasonographically guided large-core needle biopsy yielded benign pathologic results. Follow-up of more than 1 year (n = 225), results of surgical excision (n = 50), or both were obtainable in 275 (74%) of the benign lesions. No malignancies were discovered at surgical excision or during follow-up of this group of benign lesions. There were no complications related to large-core needle biopsy that required additional treatment. Ultrasonographically guided large-core needle biopsy is a safe and accurate method for evaluating breast lesions that require tissue sampling.