Polymorphisms in the apolipoprotein-E (apoE) gene may modulate lipoprotein metabolism at different steps and influence total and low density lipoprotein (LDL) cholesterol (LDLc) levels, as well as other lipid features. Population studies have documented significant differences in the frequency of apoE alleles which are related to the prevalence of various cardio-vascular and neuro-psychiatric diseases. In this study, the apoE genotypes and allele frequencies were analyzed in 216 individuals (109 dyslipidemic and 107 normo-lipidic subjects), and the relative contribution of apoE polymorphism on plasma lipid and lipoprotein levels, as well as risk factors was evaluated. In normo-lipidic volunteers, the frequencies of epsilon2, epsilon3 and epsilon4 alleles were 0.042, 0.832 and 0.126, while in dyslipidemic subjects 0.046, 0.835 and 0.119, respectively. No significant difference was observed among epsilon2, epsilon3 or epsilon4 and plasma lipid-lipoprotein levels in the dyslipidemic group. In normo-lipidemics, however, total cholesterol, LDLc and non-HDLc plasma levels were significantly lower in epsilon2 subjects when compared to epsilon3 and epsilon4 individuals. The allelic frequencies of apoE epsilon2, epsilon3 and epsilon4 were similar in dyslipidemic and normo-lipemic subjects, suggesting that apoE polymorphisms have no effect on plasma lipid-lipoprotein levels in dyslipidemic subjects. In contrast, in normo-lipemic subjects the epsilon2 allele showed to be associated with lower total cholesterol and LDLc levels, the mark of a better lipid profile. Depending on other co-existing factors, the epsilon2 allele, therefore, may play either a protective or pathogenic role. This elementary knowledge is a fundamental prerequisite for a possible diagnostic application of these lipoproteins as biomarkers to predict adverse cardio-vascular and/or neuro-psychiatric maladies.