We present a case of a 40-year-old woman, diagnosed with a flat lesion (type 0-IIa+IIc) of the colon. There was a strong suspicion for submucosal invasion, however the patient initially refused surgical intervention. Therefore, the lesion was treated with full-thickness endoscopic resection. An over-the-scope clip device was applied to seal the resulting colonic wall defect. Histological examination demonstrated a T2 adenocarcinoma, therefore the patient agreed to a left hemicolectomy. Examination of the surgical specimen demonstrated no residual neoplasia or involvement of adjacent lymph nodes. We discuss the potential advantages and limitations of this new approach, which may be indicated for patients who are not surgical candidates.