Background <p>Cerebral venous sinus thrombosis (CVST) is an uncommon cause of stroke with diverse etiologies, including inherited and acquired hypercoagulable states. Myeloproliferative neoplasms, particularly those associated with the JAK2 V617F mutation, are increasingly recognized as causes of thrombosis at unusual vascular sites and may initially present with thrombotic complications.</p> Case Report <p><?tk 2?>We report a 45-year-old Pakistani woman with hypertension and ischemic heart disease who initially presented with non-ST elevation myocardial infarction (NSTEMI) and was found to have severe left ventricular dysfunction with a large apical thrombus. She was treated with anticoagulation and discharged on apixaban. One week later, she re-presented with altered mental status and rapidly progressive deterioration in consciousness requiring intensive care support. Neuroimaging with magnetic resonance venography confirmed extensive cerebral venous sinus thrombosis with multifocal venous infarcts and hemorrhagic transformation. While the left ventricular thrombus can be explained by severe left ventricular dysfunction following NSTEMI, the occurrence of CVST at an unusual site prompted evaluation for additional prothrombotic conditions. Molecular testing revealed a JAK2 V617F mutation, consistent with an underlying myeloproliferative neoplasm. The patient improved with therapeutic anticoagulation and supportive care and was discharged on long-term anticoagulation with hematology follow-up.</p> Conclusion <p>This case highlights that unusual-site thrombosis may reflect multifactorial thrombosis, where an JAK2 V617F–positive myeloproliferative neoplasm may represent an underlying contributing prothrombotic factor. Early recognition and targeted evaluation for underlying prothrombotic disorders are essential to guide management and reduce the risk of further thrombotic events.</p>