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The objective was to describe and review the use of thrombolytic therapy in a patient with an intracranial tumor and massive pulmonary embolism. This is the first reported case of a patient with a known glioblastoma multiforme and massive pulmonary embolism who was successfully treated with alteplase. Pulmonary embolism was demonstrated by a ventilation— perfusion scan and transthoracic echocardiogram with repeat studies demonstrating resolution of the thromboembolism and reperfusion of pulmonary vasculature. A review of the literature revealed that the incidence of intracranial hemorrhage with thromboly-sis is <3% and compares favorably with the much higher mortality rate of 25% to ≥50% in patients with hemody-namically unstable pulmonary emboli. The benefit of thrombolysis may outweigh the risks of intracranial hemorrhage in these patients, and careful consideration for its use in these patients is warranted.