Although breast needle core biopsy (NCB) is now a standard diagnostic procedure in the triple assessment of screen-detected breast lesions, data on the false-positive diagnoses of malignancy (malignant NCB 'B5' with normal/benign surgery) are lacking. In this study, we have studied a large series of NCBs (101,440) to assess the causes and pitfalls resulting in false-positive NCB diagnoses and to evaluate their impact on patients' management in the screening service. Our results showed that of 40,395 malignant NCBs reported during the period of this study, 174 NCBs are considered as false-positives (0.43%; (95% confidence interval [CI] = 0.37-0.49%)). However, on review, 165 cases (95%) were found to be the result of true removal of the whole lesion in the core with subsequent negative excision biopsy samples (true-positive NCBs). This may reflect sampling of small screen detected lesions and the use of larger core biopsies at assessment. The remaining 9 cases were considered as true false-positive cores, giving a false-positive rate of 0.02% (95% CI = 0.01-0.04%). Analysis of these 9 cases showed that 8 cases, originally diagnosed as DCIS, were classified as borderline lesions or lesions of uncertain malignant potential after surgical excision. The classification and management of such borderline lesions remains controversial and diagnostic surgical excision is usually the optimum management. One case was the result of pathological misinterpretation of fat necrosis as invasive carcinoma. This was the only case that resulted in a significant over-management of the patient. In conclusion, our results showed that the true false-positive rate of NCB is extremely rare. Significant over-management of screen-detected breast lesions as a result of false-positive NCB may be considered almost nil.