While almost all animals are able to at least partially replace some lost parts, regeneration abilities vary considerably across species. Here we study gene expression patterns in distantly related species to investigate conserved regeneration strategies. To this end, we collect from the literature transcriptomic data obtained during the regeneration of three species (Hydra magnipapillata, Schmidtea mediterranea, and Apostichopus japonicus), and compare them with gene expression during regeneration in vertebrates and mammals. This allows us to identify a common set of differentially expressed genes and relevant shared pathways that are conserved across species during the early stage of the regeneration process. We also find a set of differentially expressed genes that in mammals are associated to the presence of macrophages and to the epithelial–mesenchymal transition. This suggests that features of the sophisticated wound healing strategy of mammals are already observable in earlier emerging metazoans.