We report a case of life-threatening mediastinal hematoma in a 6-mo-old girl during surgical correction of scaphocephaly. The hematoma was caused by extravascular infusion via the proximal lumen of a dislocated triple-lumen central venous catheter (CVC). Worsening symptoms of hypovolemia and ventilation problems prompted performance of transesophageal echocardiography, which reliably and quickly allowed us to exclude pericardial tamponade and detect a mediastinal hematoma. The anesthesiologist should be alert when a patient with a CVC develops acute cardiopulmonary or respiratory symptoms. Repeated aspirations of blood, especially after major positional changes and before giving large quantities of fluid or blood, should be performed to detect secondary malposition of the CVC.