PURPOSE: Unclear or suspicious breast findings are typically clarified by interventional breast biopsy. Lesions with uncertain malignant potential are grouped as B3 lesions in histopathology. The B3 group according to the European Working Group for Breast Screening Pathology (EWGBSP) comprises various breast lesions with different upgrade rates to invasive breast cancer (BC) or ductal carcinoma in situ (DCIS) if surgical removal is performed. The objective of this study was to investigate malignant upgrade rates to DCIS and/or invasive breast cancer (BC) after open surgical excision for the different B3 lesions. METHODS: A total of 192 patients with histologically verified B3 lesions were followed up retrospectively for this analysis. Patients with the B3 lesions atypical ductal hyperplasia (ADH), flat epithelial atypia (FEA), and classical lobular neoplasia (LN1-2) were combined into one group, while cellular fibroepithelial lesions (CFL) and phyllodes tumors without suspicion of malignancy, as well as papillomas and radial scars/complex sclerosing lesions (RS/CSL) were summarized in two other groups. We investigated the association of the different B3 lesions with invasive BC or DCIS after open surgical excision. RESULTS: Histopathological investigation revealed in 21 (10.9%) of the 192 patients invasive BC or DCIS after open surgical excision. The rate of patients with BC and/or DCIS significantly differed between the patient groups (p <
0.01, Fisher's exact test): The highest rate was 17.5% (95% confidence interval (CI), 10.7-26.2) in patients within the group of ADH, FEA, and LN1-2. In the other two groups, fewer malignant lesions occurred. In the group with papillomas and RS/CSL the malignant upgrade rate was 4.3% (95% CI, 0.9-12.2), while within the group with CFL and phyllodes tumors without suspicion of malignancy no malignant upgrade was observed (0.0%, 95% CI, 0.0-16.9). CONCLUSIONS: B3 lesions harbor the risk of malignant upgrade after surgical excision. In our collective ADH, FEA, and LN1-2 had significant higher upgrade rates than other B3 lesions.