A 28-year-old Chinese man diagnosed with hypercalcemic crisis was referred for Tc-99m sestamibi parathyroid imaging, which revealed a massive sestamibi-avid lesion in right-site of upper mediastinum. Contrast-enhanced CT demonstrated the lesion encroached and obstructed bilateral innominate veins and superior vena cava. Tc-99m methylene diphosphonate (MDP) bone scan and SPECT displayed ectopic uptakes in the lungs and stomach. Preoperative suspicion of parathyroid carcinoma prompted an en bloc surgery, which was confirmed in histopathology. Our case showed that although ectopic parathyroid carcinoma causing hypercalcemic crisis, extraskeletal microcalcifications, and great vessel obstruction is rare, parathyroid imaging and bone scan can help solve these diagnostic challenges.