Background: Vertebrate alpha (a)- and beta (ß)-globin gene families exemplify the way in which genomes evolve to produce functional complexity. From tandem duplication of a single globin locus, the a- and ß-globin clusters expanded, and then were separated onto different chromosomes. The previous finding of a fossil ß-globin gene (?) in the marsupial a-cluster, however, suggested that duplication of the a-ß cluster onto two chromosomes, followed by lineage-specific gene loss and duplication, produced paralogous a- and ß-globin clusters in birds and mammals. Here we analyse genomic data from an egg-laying monotreme mammal, the platypus (Ornithorhynchus anatinus), to explore haemoglobin evolution at the stem of the mammalian radiation. Results: The platypus a-globin cluster (chromosome 21) contains embryonic and adult a- globin genes, a ß-like ?-globin gene, and the GBY globin gene with homology to cytoglobin, arranged as 5'-?-?'-aD-a3-a2-a1-?-GBY-3'. The platypus ß-globin cluster (chromosome 2) contains single embryonic and adult globin genes arranged as 5'-e-ß-3'. Surprisingly, all of these globin genes were expressed in some adult tissues. Comparison of flanking sequences revealed that all jawed vertebrate a-globin clusters are flanked by MPG-C16orf35 and LUC7L, whereas all bird and mammal ß-globin clusters are embedded in olfactory genes. Thus, the mammalian a- and ß-globin clusters are orthologous to the bird a-and ß-globin clusters respectively. Conclusion: We propose that a- and ß-globin clusters evolved from an ancient MPG-C16orf35-a-ß-GBY-LUC7L arrangement 410 million years ago. A copy of the original ß (represented by ? in marsupials and monotremes) was inserted into an array of olfactory genes before the amniote radiation (>315 million years ago), then duplicated and diverged to form orthologous clusters of ß-globin genes with different expression profiles in different lineages.