Identification of conserved genomic regions between different species is crucial for the reconstruction of their last common ancestor. Indeed, such regions of conservation in today's species (if not due to chance) may either constitute stigmata of an ancestrally conserved region or result from a series of independent convergent events. The more phylogenetically distant the compared species are, the more we expect rearrangements and thus difficulties in finding regions of conservation. Here we decipher with strong evidence conserved genomic regions between vertebrates (human and zebrafish) and arthropods (Drosophila and Anopheles). This work includes a robust phylogenetic analysis in conjunction with a stringent statistical testing that allowed the significant rejection of a "by chance" conservation hypothesis. The conservation of gene clusters across four different species from two phylogenetically distant groups makes the hypothesis of an ancestral conservation more likely and parsimonious than the hypothesis of individual convergent events. This result shows that, in spite of more than 800 million years of divergence and evolution from their last common ancestor, we can still reveal stigmata of conservation between all these species. The last common ancestor of zebrafish, human, Drosophila, and Anopheles is the common ancestor of all protostomes and deuterostomes known as "Urbilateria." This study reveals clusters of probably ancestrally conserved genes and constitutes an advance toward the reconstruction of the genome of Urbilateria. Thus this work allows a better understanding of the evolutionary history of metazoan genomes, including our genome.