The lipid and lipoprotein parameters which are predominantly measured and effectively comprise the traditional lipoprotein profile include total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, and triglyceride. Total cholesterol is accepted as the initial entry point in a case finding approach such as that recommended by the National Cholesterol Education Program (NCEP). HDL cholesterol, known to be a strong inverse predicator of risk, is an additional measurement to total cholesterol to improve risk assessments. The evidence for triglyceride association remains mixed: although strong associations are found in some studies, the evidence as an independent risk factor is still incomplete. Triglyceride is therefore measured primarily for LDL estimation. Final classification and potential intervention is ultimately based on the measurement of LDL cholesterol. Reliability in the measurement of total cholesterol, HDL, LDL, and triglyceride is especially important if the uniform decision points established by the NCEP are to be properly implemented. Attention must be placed on controlling preanalytical sources of variation, which can account for as much as 60% of the total measurement variability. The major analytical source of error comes from matrix effects, which results in problems of proper analytical calibration. Instrument system calibration should be verified by a comparison with an accuracy base using fresh patient specimens. CDC has established a network of reference method laboratories to provide access to these lipid and lipoprotein accuracy bases.