In the last years, an increasing interest has been raised on non-polypoid colorectal tumors (NPT) and in particular on large flat neoplastic lesions beyond 10 mm tending to grow laterally, called laterally spreading tumors (LST). LSTs and large sessile polyps have a greater frequency of high-grade dysplasia and local invasiveness as compared to pedunculated lesions of the same size and usually represent a technical challenge for the endoscopist in terms of either diagnosis and resection. According to the Paris classification, NPTs are distinguished in slightly elevated (0-IIa, less than 2.5 mm), flat (0-IIb) or slightly depressed (0-IIc). NPTs are usually flat or slightly elevated and tend to spread laterally while in case of depressed lesions, cell proliferation growth progresses in depth in the colonic wall, thus leading to an increased risk of submucosal invasion (SMI) even for smaller neoplasms. NPTs may be frequently missed by inexperienced endoscopists, thus a careful training and precise assessment of all suspected mucosal areas should be performed. Chromoendoscopy or, if possible, narrow-band imaging technique should be considered for the estimation of SMI risk of NPTs, and the characterization of pit pattern and vascular pattern may be useful to predict the risk of SMI and, therefore, to guide the therapeutic decision. Lesions suitable to endoscopic resection are those confined to the mucosa (or superficial layer of submucosa in selected cases) whereas deeper invasion makes endoscopic therapy infeasible. Endoscopic mucosal resection (EMR, piecemeal for LSTs > 20 mm, en bloc for smaller neoplasms) remains the first-line therapy for NPTs, whereas endoscopic submucosal dissection in high-volume centers or surgery should be considered for large LSTs for which en bloc resection is mandatory and cannot be achieved by means of EMR. After piecemeal EMR, follow-up colonoscopy should be performed at 3 mo to assess resection completeness. In case of en bloc resection, surveillance colonoscopy should be scheduled at 3 years for adenomatous lesions ≥ 1 cm, or in presence of villous features or high-grade dysplasia patients (regardless of the size), while less intensive surveillance (colonoscopy at 5-10 years) is needed in case of single (or two) NPT < 1 cm presenting tubular features or low-grade dysplasia at histology.