Platypnea-orthodeoxia syndrome (POS) is an uncommon clinical condition characterized by orthostatic dyspnea and hypoxemia. The case of a female patient who manifested postoperative episodes of sudden oxygen desaturation, dyspnea, and systemic arterial hypotension following lower bilobectomy for lung adenocarcinoma was reported. After meticulous clinical investigations, the patient proved to be affected by a rare form of postural dyspnea: platypnea-orthodeoxia syndrome, a clinical disorder described in the middle of the last century. The pathophysiology was found in an intracardiac mechanism of right-to-left blood shunt, combined with lung and chest wall modification. Atrial septal defect, such as patent foramen ovale (PFO), is a common cause of platypnea-orthodeoxia syndrome; the rescue closure of PFO usually allows for an immediate and consistent improvement of the symptoms.