The platypnea-orthodeoxia syndrome is a rare clinical presentation. The differential diagnosis is short and includes cardiac, hepatic, and pulmonary causes, with right-to-left intracardiac shunt being the most common. A secondary process is usually present in conjunction with an intracardiac shunt in order for platypnea and orthodeoxia to develop. We present a 63-year-old man in whom the platypnea-orthodeoxia syndrome was associated with a patent foramen ovale and symptoms were manifested by the subacute development of pulmonary arterial hypertension mediated by pulmonary tumor emboli. On postmortem examination, the patient had an underlying poorly differentiated lung adenocarcinoma. This case provides a concise review of the platypnea-orthodeoxia syndrome and pulmonary tumor emboli and stresses the importance of looking for a secondary process in conjunction with an intracardiac shunt in establishing the underlying diagnosis.