The existence of a direct correlation between the levels of cholesterol and the production of IL-8 in the macrophage suggests some interesting hypotheses that could represent the rational basis for further studies: (a) the agonistic action of cholesterol on ERRα in CRC cells could favor the recruitment of co-regulators involved in the enhancement of IL-8 gene expression; (b) a similar mechanism could occur also in macrophages leading the way for new hypotheses on ERRα involvement in the regulation of the inflammatory process within the tumor microenvironment. The gene discussed is CXCL8; the disease is neoplasm.