Several molecular data sets suggest that acoelomorph flatworms are not members of the phylum Platyhelminthes but form a separate branch of the Metazoa that diverged from all other bilaterian animals before the separation of protostomes and deuterostomes. Here we examine the Hox gene complement of the acoel flatworms. In two distantly related acoel taxa, we identify only three distinct classes of Hox gene: an anterior gene, a posterior gene, and a central class gene most similar to genes of Hox classes 4 and 5 in other Bilateria. Phylogenetic analysis of these genes, together with the acoel caudal homologue, supports the basal position of the acoels. The similar gene sets found in two distantly related acoels suggest that this reduced gene complement may be ancestral in the acoels and that the acoels may have diverged from other bilaterians before elaboration of the 8- to 10-gene Hox cluster that characterizes most bilaterians.