Non-cirrhotic portal vein thrombosis is a rare condition. Constitutional thrombophilia, alone or with other risk factors, predisposes to splanchnic thrombosis. Methylenetetrahydrofolate reductase (MTHFR) mutations are associated with vascular diseases. We report an observation of a 48-year-old patient who was diagnosed with MTHFR mutation during the etiological workup of a mesenteric venous thrombosis.