BACKGROUND: Cryptogenic stroke constitutes approximately 40% of ischemic strokes in young adults, imposing a significant socioeconomic burden. However, the source of embolus has been specifically investigated in a few number of studies. In this report, We document the first case of a cryptogenic stroke associated with a pulmonary arteriovenous fistula (PAVF), providing evidence of mural thrombus formation within the PAVF vessel. CASE PRESENTATION: A 52-year-old woman present with sudden-onset blurriness, right-sided numbness and paresthesia, speech difficulties, and salivation. It was confirmed as embolic stroke with magnetic resonance imaging. No evidence of cerebral arteriosclerosis or stenosis was identified, and cardiogenic embolism was ruled out. Further investigation was conducted to determine the cause of the anomalous embolism. A right-to-left shunt was detected using trans-cranial Doppler and transthoracic echocardiogram. Pulmonary arteriography revealed a simple PAVF. Optical coherence tomography (OCT) was used to examine the interior structure of the fistula vessel, revealing the presence of mural thrombus and a rough endangium. CONCLUSIONS: This case provides the initial evidence regarding the location of thrombus formation assessed and raises the awareness of a potential emboligenic mechanism in PAVF.