We report an 80-year-old woman, suffering from a recurrence of a multilocalized lymphedema-associated angiosarcoma of the right arm. The tumor consisted of solid tumor cell formations and "classical" spongiform tumor complexes. In the tumor periphery, pathological endothelial cell proliferates on pre-existing dilated lymphatic capillaries were detectable, which, together with immunohistology (CD 31+/Desmoplakin-1-2.17+/CD 34-), supported the diagnosis of lymphangiosarcoma. Complete remission was achieved under radioimmunotherapy (54 Gy/Interferon beta). A further recurrence 3 months later outside the primary therapy fields was successfully treated with radiotherapy alone. During a follow-up observation period of 3 years, there was neither local recurrence nor metastasis. This case demonstrates for the first time the long-lasting efficacy of photon radiation in a case of histologically-defined lymphangiosarcoma. Further studies should elucidate the suitability of radio monotherapy as first-line therapy in lymphedema-associated angiosarcoma with lymphatic endothelium-like immunohistology.