Flat and depressed neoplasms of the colon are defined endoscopically as visible non-exophytic, flat and/or depressed mucosal lesions with a height less than half the diameter of the lesion. These neoplasms are typically smaller than their polypoid counterparts, and might be associated with a more aggressive biological behavior. While these lesions have been described in cohorts of Japanese patients for over two decades, their existence in Western populations has been less well described. This review focuses on the epidemiology and biological behavior of flat and depressed neoplasms in Western populations as well as the strategies for their identification, endoscopic staging, and therapy.