<p>Diabetes and obesity are the known partners of metabolic syndrome having co-morbidities of atherosclerosis and hypercholesterolemia. Aim is taken in this review to correlate hypercholesterolemia and carcinogenesis. A comprehensive Online survey using MEDLINE, Scopus, PubMed, Web of Science and Google Scholar was conducted for relevant journals with key search terms viz. diabetes, obesity and carcinogenesis. The information was then collated for developing this review including graphical display. Persisting vessel hypercholesterolemia may develop intracellular cholesterol saturation including cell nucleus. The intranuclear hypercholesterolemia acts as an enhancer of cell cycle activity leading to cell proliferation. An uncontrolled cell proliferation may eventually drive the system towards carcinogenesis. Atherosclerosis and carcinogenesis are found to be the Out-turn of differently regulated biphasic programming of cholesterol homeostasis between blood vessel and nuclear cavity. While atherosclerosis is an outcome of vessel hypercholesterolemia; carcinogenesis is a consequence of hypercholesterolemia in cell nucleus.</p> Graphical Abstract <p></p>