Primary mediastinal yolk sac tumors (YSTs) are rare and have a high degree of malignancy. This article reports a 42-year-old man with a primary mediastinal YST. The patient presented with chest tightness and shortness of breath. Using a contrast-enhanced computer tomography (CT) scan, the mediastinal space was found to be occupied by a mass shadow, about 10 cm × 8 cm with a clear boundary and low density. Serum alpha-fetoprotein (AFP) was elevated to 7169.66 ng/ml. The 5th day after hospitalization, a percutaneous biopsy of the mediastinal mass was performed. Malignant tumor cells were found by cytologic examination. According to the pathological morphology and immunohistochemical results, the tumor was diagnosed as primary mediastinal YST. Subsequently, the patient underwent five cycles of adjuvant chemotherapy including bleomycin, etoposide, and cisplatin (BEP) and surgical tumor removal. One month after operation, AFP was elevated to 252.96 ng/ml. CT examination showed that the tumor recurred. As of September 12, 2020, the patient has undergone four cycles of VIP (etoposide, ifosfamide, cisplatin) chemotherapy after relapse, and the patient's condition is currently in partial remission.