We report the case of a 60-year-old woman with a history of ataxia who sought evaluation after a syncopal episode. A diagnostic workup revealed pulmonary emboli, pernicious anemia (PA), hyperhomocysteinemia, and a G20210A prothrombin gene mutation. She was successfully treated with homocysteine-lowering therapy, including high doses of oral cobalamin. She also received oral anticoagulation for 6 months. At 1 year of follow-up, no further thrombotic episodes had occurred. Our report highlights the thrombotic risk of hyperhomocysteinemia secondary to PA in a patient with the G20210A prothrombin gene mutation.