An increasing number of studies now indicate that colonoscopic examination is not perfect in preventing colorectal cancer (CRC), especially of the proximal colon. Several factors can be implicated in the occurrence of interval CRCs-further referred to as postcolonoscopy CRCs-, such as missed, incompletely resected lesions and newly developed cancers. Missed lesions represent by far the dominant cause of postcolonoscopy CRCs, with nonpolypoid (flat or depressed) neoplasms and sessile serrated polyps playing a significant role. Molecular events underlying progression of such lesions may further augment the cancer risk. In this article, we review the literature about postcolonoscopy CRC risk and the most common explanations. We discuss potential implications, paying special attention to improvements required in education and training.