This study investigates aspects of the general assumption that, in bacteria, genetic variation in functionally-constrained genomic regions accumulates at a lower rate than in regions of hypermutability such as DNA repeat loci. We compared whole genome polymorphism (using high-throughput amplified fragment length polymorphism [ht-AFLP]) as well as short sequence repeat length variation (using multi-locus variable number of tandem repeat analysis [MLVA]) for 994 Staphylococcus aureus strains isolated from both healthy carriers and invasive infections. MLVA and ht-AFLP minimum spanning trees (MSTs) were similar in their identification of totally different types of genetic variants. This suggests that, despite the enhanced inherent variability of repeats, clusters of strains remain traceable. Finally, no specific molecular marker of epidemicity or virulence was identified in this large strain collection by the MLVA approach. We demonstrate that there is a difference in the rates of cross-genome mutation versus regional repeat variability in the clonal bacterial pathogen S. aureus. Despite these dynamic differences, a conservation of type assignments as based upon these two inherently different typing techniques was observed.