Hemoglobin A(1C) (HbA(1C)) is widely used for the monitoring and management of diabetes mellitus. Shortened red cell survival may result in artefactually low HbA(1C) values. In patients with hemoglobin variants or chemically-modified derivatives of hemoglobin, falsely decreased or increased HbA(1C) results may be found depending on the particular assay method. Although in most such cases, HbA(1C) can be reported if the appropriate methodology is selected. In diabetic patients with shortened red cell survival and in a small number of patients with certain hemoglobin variants, alternate approaches such as frequent glucose measurements and/or self glucose monitoring and fructosamine should be used to assess glycemic control. In diabetic patients with these conditions, HbA(1C) as the preferred diagnostic test for diabetes is not valid.