"High-performance" liquid chromatography (HPLC), applied to hemoglobin analysis, is decidely more sensitive and gives better resolution than do routine electrophoretic methods. Here we present a case with a rare double heterozygote hemoglobin S/LeporeBoston, originally diagnosed as homozygous hemoglobin S by routine electrophoretic methods. Using a gradient elution weak cation-exchange HPLC technique, we could separate hemoglobin S and hemoglobin LeporeBoston and make the correct diagnosis. This case demonstrates how HPLC can be a useful adjunct to routine electrophoresis.