We identified a male Polish patient with a very rare minor homozygous GG genotype of the tissue factor (TF) +5466A>G polymorphism, who within two months experienced a transient ischemic attack (TIA) and ischemic stroke of unknown origin associated with the presence of patent foramen ovale below 40 years of age. A relationship between the TF +5466GG genotype and cerebrovascular thromboembolic events could be explained by detectable coagulant TF activity determined in a clotting assay and increased immunoreactive TF levels detected in plasma 5 years after the previous TIA and stroke. Given the role of TF-induced pathway in blood coagulation, it might be speculated that the TF +5466A>G polymorphism, especially in the homozygous GG form, predisposes to increased risk of cerebrovascular ischemic events. There is a need to conduct a prospective study on the effect of TF +5466A>G polymorphism on the risk of cryptogenic stroke.