Laterally spreading tumors (LSTs) are increasingly recognized as important precursors of colorectal carcinoma. The clinical behavior of these large nonpolypoid lesions is still uncertain. The aim of the present study was to assess prevalence and clinico-pathological features of LSTs in a large Italian cohort of patients.The study was a subgroup analysis of a large database of patients undergoing total colonoscopy. The database originated from a multicenter cross-sectional observational study involving 80 centers throughout Italy.Data from 27,400 total colonoscopies were analyzed. Precancerous lesions were detected in 5609 patients. Of these, LSTs were identified in 254 patients (4.5%; 95% confidence interval [CI] 3.5-6.2). Granular-type LSTs (G-LSTs) accounted for 83% of the cases (211/254). LSTs were predominant in the proximal colon (154, 60.6%). A total 231 lesions were endoscopically removed, with histology being available for 242. Neoplasia was confirmed in 225 lesions (93.4%) (143 low grade adenoma, 76 high grade adenoma, and six submucosal cancer). The six cases of submucosally invasive carcinoma were diagnosed in five G-LST and one nongranular LST (NG-LST). The risk of containing advanced histology was not increased in G-LST compared with NG-LST (odds ratio [OR] 1.55, 95%CI 0.73-3.27); it was significantly higher in lesions with large nodules (OR 3.09, 95%CI 1.05-9.04; P = 0.041) or depressed surface (OR 4.27, 95%CI 1.24-14.61; P = 0.021).LSTs represent approximately 5% of all precancerous colorectal lesions in the Italian population and are prevalent in the proximal colon. These lesions are no more likely to harbor advanced histology than similar-sized polypoid lesions. Large nodularity or depressed surface are risk factors for advanced histology.