The status of the three retinoic acid receptors (RARs) alpha, beta and gamma in human colorectal cancer (CRC) has not as yet been examined. RARs are in part responsible for the actions of the retinoids (vitamin A and its derivatives), which are essential for human health and survival due to their extensive involvement in numerous cellular processes, in particular in epithelial morphology. The present study examined the expression of the three RARs in CRC using immunohisto chemical analysis of paraffin-embedded tissue sections. RAR expression in tumor (T) and adjacent non-tumor (NT) specimens from stage I (n=6), stage II (n=34), stage III (n=26) and stage IV (n=14) CRC patients was compared with that in normal mucous membranes (n=10) from control individuals. The findings were correlated with tumor grade, treatment response (progression during treatment, remission, chemoresistance) and survival as clinicopathological parameters. RAR alpha and gamma expression was decreased with CRC stage in the T tissues (P=0.016 and P=0.052, respectively), suggesting that they may be used as predictive markers. RAR beta expression in the NT tissues was associated with a more favorable prognosis (P=0.04). These results provide important information on the tumor microenvironment (the area adjacent to tumor cells).