A study in JAMA Internal Medicine suggests that we may be ‘overdiagnosising’ C. difficile in this era of molecular diagnostics. The researchers from California grouped the 1416 patients tested for C. difficile into three groups: Tox+/PCR+ (9%), Tox-/PCR+ (11%), and Tox-/PCR+ (79%) (see Figure). Perhaps unsurprisingly, compared with Tox+/PCR+ cases, Tox-/PCR+ cases had lower bacterial load, less prior antibiotic exposure, less faecal inflammation, a shorter duration of diarrhoea, were less likely to suffer complications, and were less likely to die within 30 days. Perhaps even more importantly, patients with Tox-/PCR+ were pretty much identical to patients with Tox-/PCR- specimens in all of these metrics. In short: these patients had C. difficile in their gut, but they did not have C. difficile infection. The key message here is that we should not be treating patients who are C. difficile “positive” by molecular tests only.