Preventive approaches against cancer have not been fully developed and applied. For example, the incidence of some types of cancer, including colon cancer, is highly dependent upon lifestyle, and therefore, amenable to prevention. Among the lifestyle factors, diet strongly affects the incidence of colon cancer; however, there are no definitive dietary recommendations that protect against this malignancy. The association between diet-derived bioactives and development of colonic neoplasms will remain ill defined if we do not take into account: (1) the identity of the metabolites present in the colonic lumen; (2) their concentrations in the colon; and (3) the effect of the colonic contents on the function of individual bioactives. We review two approaches that address these questions: the use of fecal water and in vitro models of the human colon. Key words: Human colon model; Fecal water; Diet; Colon cancer; Prevention; Butyrate; Polyphenols; WNT signaling Core tip: Studies on diet and colorectal cancer are in their infancy, and the relevance of many publications on the topic is questionable due to three problems: (1) there is uncertainty about which diet-derived compounds are present in the colon; (2) most studies have focused on individual bioactives; whereas, food intake results in complex metabolite mixtures; and (3) the physiological concentrations of many colonic bioactives are unknown. Here we discuss how the use of fecal water samples and in vitro models of human colon address these problems.Bordonaro M, Venema K, Putri AK, Lazarova DL. Approaches that ascertain the role of dietary compounds in colonic cancer cells. World J Gastrointest Oncol 2014; 6(1): 1-10 Available from: