Between 1996 and 2006 a total of 278 patients with soft tissue Leiomyosarcoma were treated at our centre. We identified 16 patients (5.8%) where the tumour directly arose from the blood vessels. These tumours were studied to determine their prognosis and behaviour. All tumors were in the lower limbs: 11 from the femoral vein, 3 popliteal vein, and 2 from the posterior tibial vein. Mean tumour size was 10.4 cm (3 to 33). Histological grade was high in all patients. Surgical treatment was amputation in one, excision with or without vascular reconstruction in 12 followed by radiotherapy, and 3 patients had no surgery because of advanced disease at diagnosis. Seven out of the 16 patients (44%) had metastasis at diagnosis, and five patients without metastasis at diagnosis rapidly developed metastases at a median time of 5 months from diagnosis (2–30 months). The overall survival of the patients at 5 years was 25% which was considerably worse than those with nonvascular leiomyosarcoma. We conclude that patients with leiomyosarcoma of vascular origin have a very high risk of metastases and poor prognosis when treated in the conventional way.