There is a known association between cholesterol gallstones and cancer of gall bladder (CAGB). However, the exact relation is not clear. It is proposed they are linked at molecular level by the activity of the orphan nuclear receptors (ONRs) and ABC transporter pumps involved in cholesterol and xenobiotic efflux from the liver into bile. There is evidence that these two pathways are closely interlinked and influence each other. Genetic and environmental factors that upregulate these systems can lead to the simultaneous pumping of cholesterol (which precipitate as gallstones) and a food carcinogen into the bile in gall bladder; the latter causes malignant transformation. Aflatoxin B, a potent hepatocarcinogen, could be the culprit in endemic regions such as South America and North India.