The excessive consumption of lipids is directly associated with cardiovascular problems. This is mainly attributed to saturated and trans-unsaturated lipids found in animal/vegetable fats, fried foods and partially hydrogenated oils. However, several bioactives have been reported as promotor of serum cholesterol lowering and, interestingly, they are also lipids, leading to the thesis that they must be highly biocompatible with cholesterol, explaining their hypocholesterolemic activity. This is the case of cis-unsaturated fatty acids, found in vegetable oils, and octacosanol, mainly found in rice-brain oil. Despite literature present theories on the mechanisms induced by these fatty compounds for cholesterol lowering/increasing, the physicochemical interactions between them and food cholesterol are not fully understood. Therefore, this work was aimed at investigate the changings in the cholesterol melting behavior when mixed with oleic acid, stearic acid, elaidic acid (trans-oleic acid) and octacosanol. Differential scanning calorimetry and microscopy were used to describe the complete solid-liquid equilibrium (SLE) phase diagrams. Diagrams were also modeled by SLE theory. The cholesterol melting profile was very close to the ideal behavior in all mixtures. This means that its melting temperature was decreased up to a temperature very close to pure fatty compound concentration in this order: oleic acid < elaidic < stearic acid < octacosanol. Therefore, no strong molecular interactions between these bioactives and cholesterol were observed in the liquid phase. However, when solid phase was analyzed, the SLE diagram shows that, at low concentrations of fatty compounds, cocrystals formed by cholesterol and fatty compounds were probably formed. Moreover, trans-oleic acid, highly associated to the promotion of arteriosclerosis, presented the most pronounced ability in form cocrystals with cholesterol. When cocrystals are formed, the biocompounds solubility are modified, supporting the thesis that physicochemical interactions might alters cholesterol absorption in intestinal tract or even the biochemical mechanisms in blood vessels.