This review overviews PUFA effects on tumorigenesis, the endogenous VL-PUFA synthesis pathway and enzymes, metabolites of arachidonic acid and their effects on tumorigenesis and progression of CRC, expression changes of genes involved in VL-PUFA synthesis and metabolism, and epigenetic regulation of elongase of very long fatty acid 5 (ELOVL5) in cancer. Here, ELOVL5 is linked to cancer.