A rare complication of computed tomography (CT)-guided biopsies of pulmonary lesions is systemic air embolism, with hyperbaric oxygen therapy being considered the mainstay of therapy. The authors describe the case of a 47-year-old man with a left upper lobe mass invading the chest wall who underwent CT-guided needle biopsy of a right lung base nodule to evaluate for metastatic disease. This procedure was complicated by massive systemic air embolism confirmed by CT scan. After initial resuscitative measures, the patient received on-site hyperbaric oxygen therapy and demonstrated no residual clinical sequelae from this complication.