Since the first patient with antithrombin deficiency was reported, various hereditary thrombophilia have been discovered. However, we experienced a family line of multiple thrombosis in which known hereditary thrombophilia were all refuted. Case 1 died of inferior vena cava thrombosis at the age of 56 days. Case 2, the elder sister of Case 1, developed deep vein thrombosis of the left leg at age 2. She was started on warfarin but contracted deep vein thrombosis of the right leg at the age of 7. In the family of these cases there have been another five cases of thrombosis, spanning three generations, giving a total of seven cases. Six of the cases developed at an early age, below 50 years. Antithrombin, protein C, protein S, heparin cofactor II, soluble thrombomodulin, plasminogen, alpha 2 plasminogen inhibitor, and tissue factor pathway inhibitor were measured but there were no abnormalities, nor was there any resistance to activated protein C. The onset of thrombosis in this family is becoming younger with the passing of generations, and clinical symptoms have been showing a worsening tendency.