Purpose <p>Neoadjuvant chemotherapy (NAC) is widely adopted as the standard treatment for locally advanced breast cancer. However, following NAC, tumors may become non-palpable due to complete or partial response, making it challenging to achieve adequate margins in breast-conserving surgery (BCS). Various tumor localization techniques have been developed to address this issue. This study compares traditional clip and wire-guided marking (Radiological Marking, RM) with a non-invasive technique called Topographic Sketching (TS).</p> Methods <p>This retrospective study included 208 patients who underwent BCS after their tumors became non-palpable post-NAC. A total of 102 patients underwent RM using radiopaque clips followed by wire-guided excision, while 106 patients were treated using the TS technique. In the TS group, pre-NAC imaging and physical examination were used to determine the tumor’s location, distance from anatomical landmarks, and skin projection. These data were documented photographically and archived. Post-NAC, the tumor site was re-evaluated, and the excision was guided by redrawn topographic markings based on both archival and current imaging data.</p> Results <p>Among the participants, 91 patients showed complete response and 117 showed partial response to NAC. Unifocal tumors were observed in 168 patients, and multifocal tumors in 40. Only one patient from each group required a second surgery due to positive surgical margins. During a median follow-up of five years, six patients experienced local recurrence. There were no statistically significant differences between the RM and TS groups in terms of patient age, tumor stage, nodal status, multifocality, pathological response, or molecular subtype.</p> Conclusion <p>Topographic sketching is a promising, non-invasive, and cost-effective alternative to clip and wire-guided localization. It provides critical information about the tumor’s original borders and is comparably effective in terms of surgical outcomes and recurrence rates.</p>