Background and Aims:The standard of care for resectable oesophageal cancer involves neoadjuvant chemotherapy or chemoradiotherapy followed by oesophagectomy. However, major or complete histopathologic regression (≤ypT1N0) occurs in up to 40–45% of patients treated with modern systemic regimens. In these cases, the necessity of radical surgery performed primarily to confirm complete tumour eradication is increasingly questioned. Advances in endoscopic techniques now allow local histologic evaluation and potentially curative resection of residual tumours through natural orifice approaches. To our knowledge, this is the first reported case demonstrating the technical feasibility and oncological adequacy of an organ-sparing endoscopic resection following neoadjuvant chemotherapy for locally advanced oesophageal adenocarcinoma.Methods:A 65-year-old man with locally advanced oesophageal adenocarcinoma (cT2N0M0, Siewert type II) received four cycles of neoadjuvant FLOT chemotherapy. Planned oesophagectomy was deferred after preoperative endoscopy revealed a 15-mm residual lesion at the oesophagogastric junction without endoscopic signs of invasion. The patient declined surgery and consented to local, organ-sparing endoscopic resection as part of an active surveillance strategy. The procedure was performed under general anaesthesia using an en bloc endoscopic submucosal dissection technique.Results:The resection was completed without intra- or post-procedural complications. Histopathological assessment revealed complete tumour regression with no residual adenocarcinoma (ypT0Nx) and clear resection margins (R0). Follow-up CT performed one month after the procedure showed no evidence of local or nodal disease. The multidisciplinary team subsequently recommended discontinuation of adjuvant therapy and continuation of active surveillance. At 12-month follow-up, CT demonstrated a new 6 × 16 mm para-oesophageal lymph node; endoscopic ultrasound with fine-needle aspiration confirmed reactive inflammatory changes without malignancy. At 14 months, the patient remains asymptomatic and disease-free.Conclusions:This first reported case demonstrates the technical and clinical feasibility of local, organ-sparing endoscopic resection following neoadjuvant chemotherapy for locally advanced oesophageal adenocarcinoma. Given that approximately one in five patients achieve a complete pathological response with neoadjuvant therapy, the universal requirement for oesophagectomy warrants reconsideration—particularly among multimorbid patients at high surgical risk. Local endoscopic resection enables histologic confirmation of treatment response and, in selected complete or near-complete responders, may offer curative potential within a multidisciplinary, response-adapted management strategy.