Hyperhomocysteinemia (HHC) is a known risk factor for venous and arterial thrombosis. Thrombophilia workup includes the level of homocysteine and other related parameters such as: vitamin B(12), folic acid, and methylenetetrahydrofolate reductase (MTHFR) C677T genotype. As the levels of homocysteine, vitamin B(12), folic acid, and MTHFR C677T genotype are linked biochemically, we hypothesized that a statistical association will be found between them. The purpose of the present study was to assess the association between the four parameters in patients with a thrombotic event or recurrent fetal loss. The potential study population included 326 patients who were referred to the Thrombosis and Hemostasis Unit; 125 of these patients had at least one pathological test result of the four parameters. The correlations between homocysteine and vitamin B(12) as well as between homocysteine and folic acid were found to be weak (r = -0.236 and r = -0.209, respectively). No significant difference was revealed between the mean homocysteine level and the CC, CT, and TT MTHFR genotypes (p = 0.246). In conclusion, in the population studied, the association between homocysteine, vitamin B(12), folic acid, and MTHFR C677T is weak. The results raise doubt as to whether the current routine evaluation of HHC, as part of thrombophilia workup, truly reflects the increased risk of thrombosis.