Background <p>In the case of a second ipsilateral breast cancer event (2^nd iBCE) after breast-conserving treatment (BCT), tumor histology and topography are used to distinguish between true recurrence (TR) and new primary (NP). This study aimed to address the lack of data to accurately define TR and NP.</p> Methods <p>Patients experiencing a second iBCE with a second BCT (lumpectomy + brachytherapy) were retrospectively analyzed. Histology (type, grade, hormone receptor [HR], human epidermal growth factor receptor 2 [HER2] status) and second iBCE topography were used to determine TR and NP. Oncologic outcomes of TR and NP were compared by cumulative incidence rate of second local relapse (CI-2^nd LR), distant metastasis disease (CI-DMD), disease-free survival (DFS), and overall survival (OS). A systematic literature review was performed.</p> Results <p>From September 2000 to January 2024, 113 patients met the inclusion criteria (76 TR patients, 37 NP patients). The median age was 52.1 years for the first and 65.4 years for the second iBCE. The median interval between the two breast surgeries (TI_S1S2) was 149.3 months. The second iBCE occurred at a distance from the first iBCE (82.3%), was invasive ductal carcinoma (83.2%), and had a luminal profile (92%). With a median follow-up period of 78.9 months, CI-2^nd LR was 4%, CI-DMD was 8%, DFS was 87%, and OS was 90%. No significant difference in oncologic outcome was observed between TR and NP (CI-2^nd LR: 3 vs 6% [<i>p</i> = 0.9]/CI-DMD: 9 vs 5% [<i>p</i> = 0.6]/OS: 90 vs 91% [<i>p</i> = 0.5]).</p> Conclusion <p>This study suggests that TR and NP dichotomy based on tumor histology and topography does not necessarily support TR therapeutic consequences. In case of late TR, a second BCT could be carefully discussed for patients who wish to preserve their breast.</p>