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To outline recent findings on the efficacy of n-3 polyunsaturated fatty acids in the prevention/treatment of inflammatory bowel disease and colorectal cancer.Compelling data indicate a functional link between chronic inflammation and colon cancer. With respect to environmental risk factors, there is growing evidence that long-chain n-3 polyunsaturated fatty acids found in fish oil suppress inflammatory bowel diseases and colon cancer risk in humans. Unfortunately, the molecular basis of the effect of n-3 polyunsaturated fatty acids on inflammation/colitis-associated colon cancer risk is still largely obscure. In this review, we focus on recent studies which address three emerging mechanisms of n-3 polyunsaturated fatty acids action: (1) metabolic interconversion into bioactive eicosanoids, (2) modulation of nuclear receptor activation, and (3) alteration of membrane phospholipid composition and functionality of lipid microdomains.The consumption of dietary fish oil may prove to be an effective adjuvant therapy in colon cancer. Therefore, it is both appropriate and timely to determine precisely how n-3 polyunsaturated fatty acids modulate cell signaling networks, and reduce the risk of developing colon cancer and inflammatory disorders of the intestine.