The evidence relating hypocholesterolemia to an increased risk of cancer is controversial. Although more than a dozen populations have been studied in prospective epidemiological investigations, there is relatively little consistency relating low serum cholesterol levels to future risk or mortality from cancer. Several studies have demonstrated a significant inverse relationship, but many others have failed to do so, and there is no ready explanation for the divergence of results. The data from dietary studies, both at the group level and at the individual level, indicate that, if anything, higher intakes of cholesterol appear to be related to cancer rather than lower levels. A potential role for vitamin A and for some genetic predisposition to cancer perhaps associated with lower cholesterol absorption and decreased degradation of cholesterol in the gut may possibly explain some of these inconsistencies. It is concluded that(a) the available data do not substantiate any direct cause and effect relationship between low blood cholesterol levels and cancer. Rather, the data suggest that low cholesterol levels may serve as a "marker," possibly genetic, and in only small numbers of male individuals in any given population; (b) the data do not preclude, countermand, or contradict the current public health message which recommends that those with elevated cholesterol levels seek to lower them through diets lower in saturated fat and cholesterol.