Tc-99m sestamibi has been used to detect primary brain tumors, lung tumors, and breast cancers. The authors report a patient who had superior vena cava (SVC) syndrome and underwent Tc-99m sestamibi and Tl-201 SPECT to differentiate the tumor from thrombus in the mediastinum because of an abnormal mass lesion on a contrast enhanced CT scan. An abnormal area of increased Tc-99m sestamibi uptake in the supra azygos area was demonstrated on early and delayed SPECT imaging. The washout of tumor uptake was slow. The removed tumor was confirmed to be malignant lymphoma.