OBJECTIVE To examine the histologic correlation between image-guided large-core needle biopsy (LCNB) and excisional biopsy of nonpalpable breast lesions. METHODS Histologic findings of LCNB and excision specimens were reviewed for patients who underwent image-guided LCNB of nonpalpable breast lesions from April 1, 1993, to March 31, 1996. Histologic diagnosis of the excision specimen was used as a criterion standard. Follow-up ranged from 1 to 4 years. METHODS A dedicated breast imaging clinic on the campus of an urban community hospital. METHODS Five hundred fifty-two patients with nonpalpable mammographically detected abnormalities. METHODS Histologic diagnoses of LCNB and excision specimens (part of a prospectively designed, ongoing quality audit process). RESULTS Histologic findings were benign in 389 LCNB specimens (70.5%) and abnormal in 163 (29.5%). The benign LCNB specimens remained benign on clinical and radiologic follow-up, with 1 missed malignant diagnosis. One hundred seventy-three patients underwent excision following LCNB, resulting in 10 benign and 163 abnormal specimens. Diagnoses of 102 LCNB specimens showing invasive cancer were confirmed on excision. Of 54 patients in whom LCNB specimens showed ductal carcinoma in situ (DCIS), 10 showed DCIS plus invasive cancer on excision. Of 6 patients in whom LCNB specimens showed atypical duct hyperplasia (ADH), 1 was benign, 1 showed ADH and invasive cancer, 3 showed ADH and DCIS, and 1 remained ADH exclusively on excision. The histologic diagnosis for 10 benign LCNBs remained benign after excision. Correlation coefficient was 0.93 (P < .001). CONCLUSIONS Benign disease and invasive cancer of the breast can be diagnosed with a high level of confidence using image-guided LCNB. The histologic diagnosis for patients whose LCNB specimens show ADH or DCIS may change after excision.