One of the most critical characteristics of colorectal cancer (CRC) is the difference between proximal (right-sided colon cancer, RCC) and distal (left-sided colon cancer, LCC) disease. The recent CRC studies showed the unique characteristics of RCC; RCCs were more prevalent in women than men and old patients, and the age difference between RCC and LCC was more apparent in women. Moreover, relatively poor protection against RCC by colonoscopy is a clearly hot issue for alarm. Thus, the left and right colon have been considered as dichotomous or even different organs in the view of molecular, histopathological, epidemiologic and clinical bases for over three decades. However, the evolutionary data suggesting linearity from the rectum to ascending colon beyond the simple right-left dichotomization in the views of cancer molecular features and site-specific clinicopathological differences, support the need for a paradigm shift to the colorectal continuum model rather than the traditional two-colon concept. This new multi-segmental or colorectal continuum hypothesis would provide both the better understanding of the complex etiology of colorectal carcinogenesis and the tailored preventive and therapeutic strategies for CRC including individualized CRC screening programs.