We used a nonredundant microarray of the Salmonella enterica serovar Typhimurium LT2 and Typhi CT18 genomes to assess the genomic content of a diverse set of isolates of serovar Typhi. Comparative genomic hybridization revealed 13 regions of absent or divergent gene content in the eight Typhi strains examined compared to Typhi CT18. In particular, two Typhi CT18 prophage regions, STY1048 to STY1077 and STY2038 to STY2077, as well as a five-gene islet (STY3188 to STY3193) were absent or divergent in all other Typhi strains examined. Seven Typhi strains lacked most or all of the IS1 elements present in strain CT18, and three Typhi strains lacked a P4-like phage (STY4821 to STY4834). One strain was devoid of a 149-gene region (STY4521 to STY4680), which encodes numerous phage genes and the Vi antigen biosynthesis and export gene cluster, a type IV pilus, and numerous phage genes. In Typhi strain 26T25, an amplification of an entire inter-ribosomal region encompassing 31 genes has occurred. Furthermore, a 257-gene region (STY1360 to STY1639) showed an aberrant replication pattern in three Typhi isolates. Overall, these differences in gene content indicate that even within a highly clonal bacterial population the genomic reservoir is unstable.