Heparin resistance is the failure of unusually high doses of heparin to achieve a target activated clotting time (ACT). We present the case of a 47-year-old female patient, ASA 2, who was diagnosed with a neuroendocrine retroperitoneal tumor with thrombus in the left renal vein, inferior vena cava and right atrium. General and cardiothoracic surgeons collaborated to remove the tumor under cardiopulmonary bypass. Heparin resistance was considered and treated with 1000 UI of antithrombin III concentrate. The authors review the mechanisms and management of this entity.