BACKGROUND: Whole-genome sequencing (WGS) has typically been used to confirm or refute hospital/ward outbreaks of methicillin-resistant Staphylococcus aureus (MRSA) identified through routine practice. However, appropriately targeted WGS strategies that identify routinely "undetectable" transmission remain the ultimate aim. METHODS: WGS of MRSA isolates sent to a regional microbiological laboratory was performed as part of a 12-month prospective observational study. Phylogenetic analyses identified a genetically related cluster of E-MRSA15 isolated from patients registered to the same general practice (GP) surgery. This led to an investigation to identify epidemiological links, find additional cases, and determine potential for ongoing transmission. RESULTS: We identified 15 MRSA-positive individuals with 27 highly related MRSA isolates who were linked to the GP surgery, 2 of whom died with MRSA bacteremia. Of the 13 cases that were further investigated, 11 had attended a leg ulcer/podiatry clinic. Cases lacked epidemiological links to hospitals, suggesting that transmission occurred elsewhere. Environmental and staff screening at the GP surgery did not identify an ongoing source of infection. CONCLUSIONS: Surveillance in the United Kingdom shows that the proportion of MRSA bacteremias apportioned to hospitals is decreasing, suggesting the need for greater focus on the detection of MRSA outbreaks and transmission in the community. This case study confirms that the typically nosocomial lineage (E-MRSA15) can transmit within community settings. Our study exemplifies the continued importance of WGS in detecting outbreaks, including those which may be missed by routine practice, and suggests that universal WGS of bacteremia isolates may help detect outbreaks in low-surveillance settings.