Atrial myxoma may be associated with syncope or sudden death attributed to left-sided cardiac outflow obstruction or embolization caused by tumor dislodgement or thrombus formation. Definitive treatment for primary and secondary stroke prevention is surgical resection. The role of thrombolysis in acute brain ischemia in patients with atrial myxoma is not defined. There are few data available regarding safety and efficacy of thrombolytic therapy in acute ischemic strokes caused by atrial myxoma. Prior case reports described partial success using intra-arterial local thrombolysis; however, this is invasive and can be associated with significant complications. A previously reported case of systemic thrombolysis resulted in development of cerebral hemorrhage. We describe a young man who presented with syncope and a dense stroke developing as a complication of atrial myxoma, followed by a remarkable recovery after treatment with intravenous recombinant tissue plasminogen activator and urgent cardiac surgery. Contrary to some expert opinion, systemic thrombolytic therapy may be safely and effectively used to treat acute ischemic strokes from atrial myxoma.