Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections in children have increased considerably in our area. In this study, we prospectively examined the epidemiological, clinical and molecular profile of CA-MRSA infections in children in central Greece. A total of 198 staphylococcal strains were isolated from patients with community-acquired infections over a 28-month period and 88 (44%) were found to be methicillin-resistant. Most patients with CA-MRSA had skin and soft-tissue infections (73%). Hospitalisation and surgery were more commonly required for patients with MRSA strains (p = 0.001 and p < 0.001, respectively). The presence of Panton-Valentine leukocidin (PVL) genes was identified in 28/41 (68%) CA-MRSA strains. All PVL(+) strains were found to carry a staphylococcal chromosomal cassette (SCC) mec element type IV and belonged to a single electrophoretic type similar to the European multi-locus sequence type 80 (ST80). The recent increase in CA-MRSA infections in children in our area is largely associated with the spread of the ST80 clone and their clinical characteristics are similar to those described in other parts of the world where different MRSA clones predominate.