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Abstract Background Core needle biopsy (CNB) is a standard diagnostic procedure in the setting of breast cancer screening. However, CNB may result in the borderline diagnoses of lesion of uncertain malignant potential (B3). The aim of this study was to access the outcome of lesions diagnosed as B3 category in a large series of screen-detected cases to evaluate the rates of malignancy for the different histological subtypes. Methods We identified all CNBs over a six-year period (2009-2015) in a breast cancer screening unit in Germany. A total of 8.388 CNB’s were performed for screen detected breast lesions. B3 diagnosis comprised 4.5% (376/8.388). Of the 376 patients who were diagnosed as B3, 299 underwent subsequent excision biopsy with final excision histology. Results Out of 376 patients diagnosed with B3 lesions, the prevalence of different histopathology showed 161 (42.8%) patients with atypical ductal hyperplasia (ADH), 98 (26.1%) with flat epithelial atypia (FEA), 50 women (13.3%) showed lobular neoplasia (LN), in 40 (10.6%) patients papillary findings and in 27 patients (7.2%) a radial scar complex. Final excision histology was benign in 74% (221/299) and malignant in 26% (78/299) of the patients. Lesion specific positive predictive values (PPV) for a subsequent diagnosis of in situ or invasive carcinoma were as follows: ADH 40%, FEA 20.5%, papillary lesion 13.5%, radial scar 16.6%, LN 0%. Conclusion Our results show that approximately one-third of core needle biopsies of screen detected breast lesions classified as B3 are premalignant or malignant on excision. Lesions of uncertain malignant potential of the breast (B3) are heterogeneous in respect to risk of malignancy.