Magnifying chromoendoscopy is an exciting new tool that allows detailed analysis of the morphological archi- tecture of mucosal crypt orifices. In this review, we principally describe the efficacy of magnifying chromoen- doscopy and magnifying colonoscopy with narrow band imaging (NBI) for differential diagnosis of colorectal lesions, including distinction between non-neoplastic and neoplastic lesions, and also between endoscopically treatable early invasive cancers and untreatable cancers, based on a review of the literature. We have con- ducted a prospective study showing that a combination of magnifying colonoscopy and chromoendoscopy is currently a more reliable method than conventional endoscopy and chromoendoscopy for separating non-neo- plastic from neoplastic lesions of the colon and rectum. Magnifying colonoscopy with NBI is convenient and as accurate as chromoendoscopy with magnification. We principally use only magnifying colonoscopy with NBI, rather than chromoendoscopy, to routinely distinguish neoplastic from non-neoplastic polyps. Colonoscopists can predict the depth of invasion of early colorectal cancer by magnifying chromoendoscopy, magnifying colonoscopy with NBI and the non-lifting sign. Among these approaches, magnifying chromoendoscopy is diagnostically the most reliable, with an accuracy, sensitivity, and specificitiy of 98.8%, 85.6%, and 99.4%, respectively. Although its reliability depends on the skill of magnifying observation, widespread applications of the magnification technique could influence the indications for biopsy sampling during colonoscopy and the indications for mucosectomy.