OBJECTIVE To determine what factors are associated with unsuccessful needle-localized breast biopsy (NLBB). METHODS Findings in 280 consecutive nonpalpable breast lesions in 262 women (age range, 27-87 years; mean age, 55 years) who underwent nonstereotactic, mammographically guided, standardized NLBB were retrospectively analyzed according to mammographic lesion type, lesion size, number of lesions per breast, needle type, proximity of needle to lesion, radiologist, specimen size, surgeon, and histologic findings. RESULTS Biopsy failed in seven (2.5%) of 280 lesions. Failures were related to lesion type, lesion size, number of lesions per breast, accuracy of needle placement, and volume of tissue removed. Removal of more than one tissue specimen converted failure to success in 14 (67%) of 21 initially missed lesions, all microcalcifications. CONCLUSIONS Unsuccessful NLBB was more likely with two lesions per breast, small lesions, small specimens, and microcalcifications. Piercing such lesions with the localizing needle led to successful biopsy. Removal of more tissue was helpful with missed microcalcifications.