Enterohemorrhagic Escherichia coli(EHEC) causes diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome. Genomic comparison of an EHEC O157: H7 strain isolated from the Sakai outbreak and a benign laboratory strain K-12 revealed that acquisition of a large amount of foreign DNA has promoted the genetic diversification of E. coli strains. In the emergence of O157: H7, bacteriophages, in particular, played an important role. EHEC are a group of strains with several serotypes, each belonging to different E. coli lineages. Even in an O157 lineage, significant phenotypic and genetic heterogeneities are observed. Recent knowledge on the significance and the generating mechanism of such heterogeneity in EHEC strains are summarized.