Cryptogenic stroke (CS) is common, as is patent foramen ovale (PFO). By chance, they overlap frequently. However, if the relationship was just chance, then PFO prevalence in patients with CS would match the general population (approximately 25%). But PFOs are overrepresented in the CS population (approximately 50%). Paradoxical embolism explains this association—the paradox being a venous source thrombus appearing in an artery (via right-to-left shunt). Because of the high background prevalence, a discovered PFO only has a 50:50 chance of actually causing the stroke in an individual patient.1 The physician asks, “Is the PFO relevant? If I can’t know, then why should I look?” Ergo, diagnostic nihilism.