Sphingomyelin metabolism generates anticancer signals such as ceramide and sphingosine that may inhibit cell proliferation, and induce differentiation and apoptosis. Changes of sphingomyelin metabolism are found to be associated with tumorigenesis in various tissues and a particular link between sphingomyelin metabolism and colon cancer has been indicated. The effects of several anticancer drugs on sphingomyelin metabolism have been examined recently and there is an increasing interest in discovering new drugs taking sphingomyelin as a target. The present review outlines the sphingomyelin metabolism pathway, introduces the evidence linking sphingomyelin to colon cancer, and summarizes the anticancer drugs and dietary factors that affect the metabolism of sphingomyelin and, thus, the production of the anticancer messengers in the colon.