Background/Aim: Clinicopathological features of patients undergoing margin enlargement after lumpectomy for early breast cancer with positive/close excision margins were analyzed in order to define whether a re-operative procedure could have been avoided. Furthermore, a standardized protocol of specimen orientation was adopted in order to optimize both the widening procedure as well as the oncologic outcome. Patients and Methods: A retrospective analysis was performed including pre-, peri-, and post-operative parameters, and a predictive score by means of a multivariate model was developed using all clinically and statistically significant variables associated with residual disease (RD). Results: RD was significantly related to positive tumor margins, hormone receptor negative, HER2-positive, and tumors with high Ki67 proliferation index (p3, only 2 patients (2.0%) had RD, while in 81 patients with a score ≤3, 55 patients (67.9%) had RD (p