We describe a case of greater saphenous vein thrombosis in a 50-year-old previously healthy man, occurred only 3 weeks after starting testosterone (T) replacement therapy (20 mg/day, gel) for hypergonadotropic hypogonadism. There were no clinical known risk factors for thrombosis. Laboratory assessment of thrombophilia, performed later, revealed only methylenetetrahydrofolate reductase (MTHFR) A1298C polymorphism. On the basis of other recently reported cases, we suppose a relationship between androgenic therapy and venous thrombosis. We suggest the same caution before starting T replacement therapy in male as in female administration of estrogens.