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Background/Aim: Patients with Stage I-II breast cancer undergoing breast-conserving surgery after neoadjuvant chemotherapy (BCS-NAC) were retrospectively assessed in order to evaluate the extent of a safe excision margin. Materials and Methods: Between 2003 and 2020, 151 patients underwent risk-adapted BCS-NAC; margin involvement was always assessed at definitive histology. Patients with complete pathological response (pCR) were classified as the RX group, whereas those with residual disease and negative margins were stratified as R0 < 1 mm (margin < 1 mm) and R0 > 1 mm (margin > 1 mm). Results: Totals of 29 (19.2%), 64 (42.4%), and 58 patients (38.4%) were included in the R0 < 1 mm, R0 > 1 mm, and RX groups, respectively, and 2 patients with margin involvement had a mastectomy. Ten instances of local recurrence (6.6%) occurred, with no statistically significant difference in local recurrence-free survival (LRFS) between the three groups. A statistically significant advantage of disease-free survival (p = 0.002) and overall survival (p = 0.010) was observed in patients with pCR. Conclusions: BCS-NAC was increased, especially in HER-2-positive and triple-negative tumors; risk-adapted BCS should be preferably pursued to highlight the cosmetic benefit of NAC. The similar rate of LRFS in the three groups of patients suggests a shift toward the “no ink on tumor” paradigm for patients undergoing BCS-NAC.