OBJECTIVES Primary mediastinal myelolipoma (PMM) is a rare benign tumour composed of haematopoietic tissue and mature adipose tissue. Here, we report the largest series aiming to investigate the outcomes of surgical treatment for patients with PMM. METHODS We retrospectively reviewed the data of 12 patients operated in a single institute during the period between April 2008 and December 2014. RESULTS There were 7 female and 5 male patients between 54 and 73 years old (median age, 64 years). Among them, 11 patients underwent unilateral (n = 10) or bilateral (n = 1) mass resection via video-assisted thoracic surgery (VATS), and 1 patient underwent a planned open thoracotomy due to a large tumour volume. The VATS operating time ranged from 20 to 65 min (median, 30 min) and intraoperative blood loss ranged from 20 to 60 ml (median, 30 ml). The open thoracotomy operating time was 120 min, and the blood loss was 1000 ml; thus, the patient received blood transfusion (2 units of RBCs). No operative mortalities or major postoperative complications were observed. All patients experienced a regular follow-up ranging from 2 to 80 months with a median follow-up of 18 months. No recurrence was observed at the time of evaluation. CONCLUSIONS Surgical treatment is recommended for the diagnosis and treatment of PMM, while VATS is a safe and feasible option in most cases.