Over the past few years, the methodologies used for the identification of hemoglobin A variants have been greatly improved. Both the protein- and DNA-based strategies have their own advantages and limitations. In this report we illustrate the use of both assays for the characterization of a hemoglobin Cocody variant in a women of Spanish descent. After evaluating the mobility value matrix of the abnormal hemoglobin, the amino acid transition was determined by HPLC and micro-sequencing of the protein. The beta 21 Asp was shown to be substituted by an Asn. At the DNA level, the only nucleotide replacement responsible for this amino acid substitution is GAT--->AAT at codon 21. The analysis of the beta-globin gene by denaturing gradient gel electrophoresis (DGGE) method showed that the mutation was situated in a fragment including exon 1. The hemoglobin variant was then identified to be hemoglobin Cocody by DNA sequencing of this fragment.