Background: This study evaluates the underestimation rate of papilloma lesions diagnosed with vacuum-assisted breast biopsy (VABB), taking into consideration the greater volume excised. Patients and Methods: 56 women with a diagnosis of a papilloma lesion after VABB (Mammotest; Fischer Imaging, Denver, CO, USA) were evaluated. At least 24 cores were excised in all cases (mean 74, range 24–96 cores) and a preoperative diagnosis was established. Subsequently, open surgery using hook-wire localization followed. A second, postoperative diagnosis was independently and blindly made. The association between the pathological types and Breast Imaging Report and Data System (BI-RADS) classification, as well as the discrepancy between preoperative and postoperative diagnoses, was evaluated. Results: The underestimation rate of papillary lesions was 3.6%. When the papillary lesions did not coexist preoperatively with any other precursor breast lesions, the underestimation rate was 0%. The underestimation rate did not differ with age, BI-RADS category or type of lesion. Conclusion: Conservative management of patients with a papillary lesion diagnosis may follow when the extended VABB protocol is adopted and a great tissue volume is excised. However, when diagnosing a coexisting papillary lesion with a precursor breast lesion, open surgery should follow, given the high probability of a postoperative cancer diagnosis.