Endoscopic full-thickness resection (EFTR) is a new technique for the resection of colonic lesions with limitations for other techniques such as endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) due to fibrosis, the location of the lesion or invasion depth. In addition, techniques such as ESD require a long learning curve and unfortunately they are not fully implemented in Western countries. EFTR has numerous indications, which are expanding daily. The Full-Thickness Resection Device® (FTRD) is a promising tool, although it has many limitations and is associated with some risks. One of the main limitations of this resection device is the size of the lesion and it is not recommended for the resection of lesions > 30 mm. Furthermore, tumor size is directly related to the "en bloc" resection rate. On the one hand, this case report suggests that neoadjuvant chemotherapy can modify the lesion size and larger lesions become candidates for EFTR in a second attempt. On the other hand, the concomitant use of systemic anticancer therapy could be a contraindication for the use of FTRD® as it may be associated with late perforations. It is necessary to establish the time between the use of chemotherapy and the use of FTRD® in order to avoid complications. These considerations must be analyzed in future prospective studies.