Molecular typing was performed to reveal the genetic diversity among Staphylococcus aureus strains causing deep-seated versus superficial staphylococcal infections. Pulsed-field gel electrophoresis with cluster analysis, plasmid and antimicrobial susceptibility profiling of 50 S. aureus strains collected from these 2 groups of patients were undertaken. A total of 19 (designated A through S) distinct genotypes were identified by PFGE of Sma I-digested genomic DNA. The most prevalent PFGE type was L, which accounted for 30% of isolates and was detected among superficial isolates only. The second most prevalent PFGE type, type A (18%), was predominant among deep-seated isolates. Remaining PFGE types varied in distribution between the 2 groups. Plasmid profile analysis revealed that deep isolates harbour plasmids more frequently (comprising 64% of isolates) than superficial isolates (4%) and showed 10 and 2 distinct patterns, respectively, with pattern 1 being the dominant among deep isolates. Antimicrobial susceptibility data suggested an increased prevalence of antibiotic resistance among deep isolates with the majority (40%) exhibiting identical antibiograms compared to superficial isolates. No resistance was detected against clindamycin and vancomycin. The results of our study indicate a previously unrecognized dichotomy of S. aureus strains, causing deep-seated and superficial infections.