EPS8 codes for a protein essential in Ras to Rac signaling leading to actin remodeling. Three genes highly homologous to EPS8 were discovered, thereby defining a novel gene family. Here, we report the genomic structure of EPS8 and the EPS8-related genes in human and mouse. We performed BLASTN searches against the Celera Human Genome and Mouse Fragments Database. The mouse fragments were manually assembled, and the organization of both human and mouse genes was reconstructed. The gene structures in Celera annotations of the human and mouse genomes were compared to outline correspondences and divergences. We also compared the EPS8 family gene structures predicted by Celera with those predicted by NCBI. Moreover, we performed a virtual analysis of the expression of the EPS8 gene family members by using the SAGEmap Database in NCBI. Finally, we analyzed the domain organization of the gene products and their evolutionary conservation to define novel putative domains, thereby helping to predict novel modality of action for the members of this gene family. The data obtained will be instrumental in directing further experimental functional characterization of these genes.