Key Clinical MessageThere are limited published cases of primary mediastinal yolk sac tumor (PMYST), with no consensus on the best treatment alternative. By far, the surgery oriented comprehensive therapies are the main treatment methods. The surgical strategy should be individualized and aimed at radical resection, considering all the possibilities, including the use of cardiopulmonary bypass and prosthetic materials.AbstractA 15‐year‐old boy was diagnosed as PMYST. The tumor, with a size about 13 × 12 × 8 cm, was located in the right upper mediastinum, closely adhering to ascending aorta, superior vena cava, right atrium, and the right hilum. After 6 cycles chemotherapy of bleomycin, etoposide, and cisplatin (BEP), no significant change was found in the size of tumor. Subsequently, an extended tumor excision including partial resection of the right lung, the pericardium, the diaphragm and the right phrenic nerve, was performed successfully with cardiopulmonary bypass on standby. During 6 months of follow‐up, there was no tumor recurrence. Meanwhile, in PubMed, we searched the English case reports and case series of PMYST during the past decade. A total of 73 articles were retrieved, in which 22 articles on the therapy and prognosis of PMYST were extracted and reviewed, included 16 case reports and 6 case series with a total of 52 patients. Due to the rarity of PMYST, it is difficult to provide a specific treatment regimen. The surgery‐oriented comprehensive therapies are still the main treatment methods. The surgical strategy should be individualized and aim at radical resection, considering all the possibilities, including the use of cardiopulmonary bypass and prosthetic materials.