Although it is estimated that > 1 billion passengers travel by air worldwide each year, the incidence of in-flight emergencies is low. However, due to nonstandardized reporting requirements for in-flight medical emergencies, the true incidence of pulmonary barotrauma in airplane passengers is unknown. We describe the case of a passenger with an asymptomatic intrapulmonary cyst in whom a severe case of cerebral gas embolism developed during an aircraft flight. The decrease in ambient pressure during the aircraft climb resulted in expansion of the cyst volume based on Boyle’s law (pressure × volume = constant). Due to the cyst expansion, we believe tears in the wall led to the leakage of air into the surrounding vessels followed by brain gas emboli. Adult patients with intrapulmonary cysts should be strongly considered for cyst resection or should at least be advised to abstain from activities leading to considerable changes in ambient pressure.