Cancer of left and right colon has a differing prevalence at varying ages, in high- and low-incidence nations, as well as in men and in women. There also is a difference in clinical presentation, in prognosis, and possibly in genetic and environmental epidemiology. This review proposes that cancers of proximal and distal colon are different tumors because of their embryologic origin, genetic changes, and biologic identity. These factors are important in understanding the 'shift of tumors from more distal to more proximal sites in the colon' and in evaluating potential suggestions for instituting advances in diagnosis and prevention.