A 70-year-old former shipyard worker presented with dyspnea and edema of the upper thorax suggesting the diagnosis of superior vena cava syndrome. Further evaluation revealed mesothelioma with both epithelial and spindled histologic patterns. The extensive mesothelioma had invaded the adventitia of the superior vena cava, the pleura of the lungs bilaterally, the superficial myocardium, and the liver. A terminal hyercoagulable state with great vein thrombosis was also contributory. To our knowledge this is the first documented case of superior vena cava syndrome associated with malignant mesothelioma.