Abstract. Colorectal cancer (CRC) is considered to develop through the conventional adenoma-carcinoma sequence. However, the existence of de novo carcinogenesis, without any intervening precursor lesions, has been suggested for certain morphologically different tumors lacking polypoid characteristics. The presence of such tumors, along with their correlation with cardinal clinicopathological parameters, such as stage, grade and site, was retrospectively investigated in a series of 119 surgically treated CRC cases. The absence of particular polypoid characteristics (adenomatous remnants or coexisting polyps in the tumor vicinity) in combination with an infiltrative (or ulceroinfiltrative) growth pattern, were the criteria defining the nonpolypoid origin. The recorded frequencies of remnants, coexisting polyps and infiltrative tumors were 7, 5, 9 and 32%, respectively. The incidence of cases meeting the above-mentioned criteria was 28.5%. These nonpolypoid lesions exhibited a predilection for proximal anatomical site (P=0.04), probably associated with their infiltrative pattern. Most importantly, de novo lesions (unlike polypoid) were rarely found among cases with indolent tumor characteristics (stage I or grade I, P=0.008), showing a considerably different overall pattern of distribution by stage and grade as compared to that of polypoid tumors (P=0.03). The fact that nonpolypoid CRCs appeared to be clinicopathologically different from their polypoid counterparts is supportive of possible de novo origin and suggestive of a likely worse clinical behavior. The impact of these findings should be investigated to determine potential applications in the diagnosis, treatment and surveillance of these lesions.