Rationale:Surgical removal of a giant mediastinal lipoma or liposarcoma involving both chest cavities is always challenging.Patient concerns:We present 2 cases of giant mediastinal tumor, one of which was a 22-year-old female who was admitted to our hospital due to a mild dyspnea after running. Computed tomography (CT) scan revealed a large mass with low density occupying the entire right hemithorax and extending anteriorly into the left. The other patient was a 43-year-old male, who was presented to the hospital with complaints of gradually progressive dyspnea. CT scan revealed a mass comprised of fat density with areas of soft-tissue density in-between, involving in both chest cavities, draping around the heart and great vessels.Interventions:Both of the patients receive complete resection through a standard median sternotomy.Diagnoses:Histologic examination revealed lipoma for the first patient, and well differentiated liposarcoma for the second.Outcomes:Both of their symptoms were improved after surgery and the postoperative courses were good.Lessons:Our experience indicated that complete surgical removal through a standard median sternotomy is a safe and efficient approach for the treatment of giant mediastinal lipoma and liposarcoma.