The arrangement of Hox genes into physical clusters is fundamental to the patterning of animal body plans, through the phenomenon of colinearity. Other homeobox genes are often described as dispersed, implying they are not arranged into clusters. Contrary to this view, however, two clusters of non-Hox homeobox genes have been reported: the amphioxus ParaHox gene cluster and the Drosophila 93D/E cluster (referred to here as the NKL cluster). Here I examine the antiquity of these gene clusters, their conservation and their pattern of evolution in vertebrate genomes. I argue that the ParaHox gene cluster arose early in animal evolution, and duplicated in vertebrates to give the four clusters in human and mouse genomes. The NKL cluster is also ancient, and also duplicated to yield four descendent clusters in mammalian genomes. The NKL and Hox gene clusters were originally chromosomal neighbours, within an ancient and extensive array of at least 30 related homeobox genes. There is no necessary relationship between clustering and colinearity, although it is argued that the ParaHox gene cluster does show modified spatial colinearity. A novel hypothesis for the evolution of ParaHox gene expression in deuterostomes is presented.