The amount and type of dietary fats represent risk factors for several cancers. Essential PUFAs serve as precursors of several biologically active molecules, mainly endocannabinoids and eicosanoids, which participate in tumorigenic processes. However, their mechanisms still remain unclear. This article reviews the current knowledge and experimental results on the effects of dietary manipulation of n-3, n-6 essential fatty acids (EFA) including the conjugated linoleic acid (CLA), on eicosanoid and endocannabinoid production, and their correlation with cancer development. The oxidative pathways of Arachidonic acid (AA) when it is released from phospholipids as Lipoxygenases (LOXs), cyclooxygenases (COX) and Cytochrome P-450s (CYP450) to eicosanoids, and the non-oxidative pathway to endocannabinoid synthesis are summarized. COXs, LOXs, and CYP 450s, endocannabinoids, thereby generating oxygenated products that resemble eicosanoids with the slight difference that endocannabinoid-derived products retain amide or ester functionalities at C1. Competition between n – 3 and n – 6 FA families gives rise to a variation in the ratio of the eicosanoid products, but the significance of these changes are as yet poorly understood. Finally, we propose that the apparently contradictory results in the field of eicosanoids, endocannabionids and cancer should be considered due to difficulties arising from the lack of nutritional evaluation.