We describe the first reported case of a thrombophilia patient genetically homozygous for a recently described polymorphism in the 3'-UTR (untranslated region) of the prothrombin gene. It has previously been demonstrated that this genetic variant due to a G to A transition at nucleotide 20210 is common and associated with an almost threefold increased risk of venous thrombosis. This polymorphism was also shown to be associated with elevated plasma prothrombin (factor II) levels, which in itself was found to be a risk factor for venous thrombosis. The patient was a healthy young Mexican male who presented with a myocardial infarction and subsequent ileofemoral venous thrombosis and massive saddle pulmonary embolus. Testing done during his initial hospitalization suggested a congenital protein C deficiency. The patient was found to be homozygous for the prothrombin gene polymorphism as well as a carrier for factor V Leiden. This case strongly implies a clinically significant role for the factor II gene mutation in both arterial and venous thrombosis and demonstrates the need to perform diagnostic clotting based assays after resolution of acute thrombotic events. These findings further support the 'double hit' theory for thrombophilia in young patients.