To illustrate this, a 50-year-old male, resident of Guwahati, Assam (North-east part of India), known case of type 2 diabetes mellitus for last 8 years, presented to our Out-Patient Department for the Management of Diabetes Mellitus. He had osmotic symptoms in the form of polyuria and polydipsia at presentation. His physical examination revealed no abnormality except for mild splenomegaly. Laboratory parameters revealed fasting plasma glucose of 240 mg/dL and 320 mg/dL 2-h after breakfast. The HbA1C was not readable by ion-exchange high-pressure liquid chromatography (HPLC) and remained undetected on a repeat test from another laboratory using ion-exchange HPLC. Hemoglobinopathy was suspected as a probable cause, as the patient was from North-east area of India, where this condition is relatively more common.[8] Hb electrophoresis was ordered which revealed Hb A of 14.8% (normal range: 94.3–98.5%), Hb E of 82.8% (normal range: 0.00%) and Hb F of 2.4% (normal range: 0–2%). HbA1C could not be detected as Hb A2, and HbA1C co-eluted at the same time and could not be separated. Hb E disease was diagnosed (homozygous state). Then HbA1C was measured using immunoassay technique (point-of-care apparatus) and was found to be 6.4%. However, with the plasma glucose readings that were obtained, expected HbA1C was higher. Serum fructosamine was 395 μmol/L (normal range: 202–282 μmol/L) that was corresponding with high glycemia and not with the reported HbA1C level. Serum Hb level was found to be 10.2 g/dL accounting for mild anemia. He has a 16-year-old daughter with a history of low Hb (Hb = 8.8–10.5 g/dL). Hb electrophoresis revealed Hb E disease in her as well.