•Lepore Hemoglobin is a structurally abnormal type of haemoglobin consisting of an abnormal globin chain which is a hybrid or fused globin chain comprising an N-terminal amino acid sequence of a delta chain and the C-terminal amino acid sequence of a beta chain.•The synthesis of these hybrid chains is substantially less than that of the β-chains, resulting in an overall reduction in the non-α globin chains and patients present with a clinical picture of haemolytic anemia.•But Hb Lepore can be differentiated from β-Thalassemia by the presence of a distinct Hb Lepore band on cellulose acetate electrophoresis or quantification in High Performance Liquid Chromatography (HPLC).•Presumptive diagnosis can be made in lab by a multi-faceted approach consisting of a series of blood count/red cell indices, Hb electrophoresis and haemoglobin analysis by HPLC. Quantitative analysis for any Hb variant disorder is made by HPLC better than Hb Electrophoresis, the same was done in our case report.
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