BACKGROUND: Systemic air embolism is recognized as a potentially fatal but extremely rare complication following percutaneous transthoracic needle biopsy. However, its incidence might be underestimated by missing systemic air in patients without cardiac or cerebral symptoms. METHODS: This study was based on four cases (one man and three women; age range, 54 to 75 years) of systemic air embolism complicating CT scan-guided transthoracic needle biopsy, which were encountered among 1,010 procedures performed at our institution from April 1999 to December 2006. The target lesion was a lung tumor in three patients, and a mediastinal tumor in one patient. The procedure was performed percutaneously under CT scan-fluoroscopic guidance by using a coaxial biopsy needle system. RESULTS: In all four patients, a specimen was successfully obtained from the lesions. During or immediately after the procedure, all patients experienced paroxysms of coughing. In three patients without cardiac or cerebral symptoms, the presence of systemic air was confirmed on postprocedural CT scan images; it was resolved without causing morbidity after the immediate therapy. The presence of systemic air was missed in one initially asymptomatic patient, resulting in a subsequent neurologic deficit. CONCLUSIONS: Systemic air embolism following CT scan-guided transthoracic needle biopsy was encountered more frequently than would be expected. The considerable attention we gave to this complication enabled us to recognize it in patients without cardiac or cerebral symptoms. No sequelae were observed in the three patients in whom systemic air embolism was detected, and the therapy was initiated immediately, whereas missing systemic air led to cerebral embolism in one patient in our four cases.