A DNA microarray was designed for the genotyping of S. aureus covering about 180 genes and 300 alleles thereof. This included species-specific controls, accessory gene regulator (agr) alleles, genes encoding virulence factors and microbial surface components recognising adhesive matrix molecules (MSCRAMMs), capsule type-specific genes, as well as resistance determinants. An assay based on linear multiplex DNA amplification and array hybridisation was applied to approximately 1500 isolates from animals and humans, including patients as well as healthy controls. Beyond assessment of virulence and drug resistance, a good correlation of hybridisation patterns and multilocus sequence typing (MLST) was found. Phylogenetic trees were constructed from hybridisation profiles showing that, indeed similarity of hybridisation patterns corresponded to phylogenetic relatedness. Thus, isolates can be assigned to strains and to clonal complexes based on recognition of hybridisation patterns. While the overall hybridisation profiles of different isolates within a strain proved to be stable, frequent random gene deletions or acquisitions were observed affecting not only genes on mobile elements but also core genome targets such as MSCRAMM genes. Thus, epidemic strains or spa-types cannot be regarded as genetically homogenous units, but rather as a clusters of related, but changeable genotypes. This phenomenon has been observed for several major epidemic strains. The potential of this variability for typing purposes and outbreak surveillance is under investigation.