One home-developed assay and two commercial assays for the rapid identification of methicillin-resistant Staphylococcus aureus (MRSA) were compared by use of a collection of clinical isolates displaying highly diverse genetic backgrounds. Our results suggest that users of orfX-staphylococcal cassette chromosome mec-based assays should repeatedly monitor the local epidemiology to minimize the risks of detection bias and the omission of emerging MRSA clones.