We present the case of a 56-year-old woman with an anterior mediastinal tumor who has past history of myasthenia gravis and invasive thymoma. Furthermore, she had superior vena cava syndrome that was caused by a rapidly growing tumor. A biopsy proved diffuse large B-cell lymphoma. After 8 courses of chemotherapy, remission of the lymphoma was achieved. Because a second primary malignancy, including lymphoma, can occur in patients with thymoma, a biopsy is necessary for tumors located in the anterior mediastinum, particularly in patients with a history of treatment for thymoma, to distinguish between recurrence and a second primary malignancy.