Vertebrate and Drosophila Iroquois genes are organized in clusters of 3 genes sharing blocks of conserved regulatory sequences. Here, we report a 3-gene cluster in the basal, preduplicative chordate amphioxus. Surprisingly, however, the origin of the amphioxus cluster is independent of those in vertebrates and drosophilids. Investigation of genomic organization of Iroquois genes in other 17 metazoan genomes revealed a fourth independent 3-gene cluster organization in polychaetes, as well as additional 2- and 4-gene clusters in other clades, in one of the most striking examples of convergence in genomic organization described so far. The recurrent independent evolution of Iroquois clusters suggests a functional importance of this organization for these genes, perhaps related to the sharing of regulatory elements. Consistent with this, comparative analysis of genomic regions flanking the 3 amphioxus Irx genes revealed several blocks of sequences, conserved for at least 100 Myr. Finally, we discuss the possible causes and implications of the convergent evolution of this genomic and regulatory organization throughout metazoans.