Pericardial cysts (PCs) are uncommon benign congenital anomalies residing in the middle mediastinum. The location of PCs is diverse with 70% of cases in the right cardiophrenic angle, 22% in the left cardiophrenic angle, and 8% in the posterior (as in our case) or superior anterior part of the mediastinum. In 2019, a 54-year-old woman was referred to the emergency department of Imam Khomeini Hospital Complex (Tehran, Iran) suffering from progressive shortness of breath. The chest computed tomography scan showed an unusual giant cystic lesion occupying >50% of the right hemithorax. The cystic lesion was primarily located in the posterior mediastinum. The patient underwent video-assisted thoracoscopic surgery (VATS), and the cyst was completely resected from the mediastinum. During past decades, several cases of PCs have been reported in different age and sex groups. Here, we present a case of a giant pericardial cyst (PC) located in the posterior mediastinum. The cyst was successfully resected using VATS. Only one other study has reported a PC in the posterior mediastinum.