Staphylococcus aureus was isolated in 88 (30.8%) of 286 adult patients suffering from various skin and soft-tissue infections examined in the outpatient department of a 650 bed tertiary-care hospital of Athens, Greece between January 2006 and December 2007. Twenty-seven (30.7%) of the S. aureus infections were caused by methicillin-resistant S. aureus (MRSA). All MRSA isolates were also resistant to tetracycline, fucidic acid and kanamycin, but were sensitive to gentamicin and tobramycin, as well as to to cotrimoxazole, chloramphenicol, quinolones, clindamycin and erythromycin. All isolates belonged to staphylococcal cassette chromosome mec elements (SCCmec) type IV, and were found to carry the lukF-PV and lukS genes coding for Panton-Valentine leukocidin (PVL). Pulsed-field gel electrophoresis (PFGE) and spa-typing revealed high genetic similarity among all MRSA isolates and with the PFGE pattern of the well-described ST80 clone that seems to be spreading through Europe. The high prevalence of MRSA among S. aureus infections in the community signify that empiric therapy in Greece, when clinically indicated, should exclude beta-lactam antibiotics. Moreover, the establishment of an active screening for PVL-positive community-acquired (CA)-MRSA carriage and the adoption of a search and destroy strategy for CA-MRSA in all patients admitted with purulent skin and soft-tissue is of high priority in Greece as well as in all European countries which face high rates of CA-MRSA infection.