Angiosarcomas of the breast (ASB) are rare, representing <1% of breast malignancies. They can develop as a primary or secondary malignancy, also called post-radiation angiosarcoma. The aim of the this study is to discuss diagnosis, treatment, and outcome of primary and secondary ASB patients, diagnosed and treated in a single institution, over a 10-year period and to further compare the two conditions. We retrieved 28 consecutive cases of ASB, diagnosed from 1999 to 2009 at the European Institute of Oncology. Clinical and pathologic findings and survival analyses were performed. Of the 28 cases (27 women and 1 man), eight were primary breast angiosarcomas (PBA) and 20 were secondary breast angiosarcomas (SBA). Median follow-up was 23 months (range 1-112 months). Type of treatment (conservative or radical surgery) did not affect survival in both types of angiosarcomas. The clinical course observed was characterized by a high rate of local recurrence rather than distant metastasis or death from disease. There was a correlation between histological grade and prognosis of angiosarcomas with high-grade tumors presenting worse prognosis. SBA had a poorer prognosis compared to PBA. Our data indicate that primary and secondary ASB are distinct clinical and pathological features. SBA showed worse prognosis and was more often diagnosed in the study period compared to PBA. Physicians who care for patients who have been treated with radiation must be aware of its potential to induce angiosarcoma and stay vigilant in its detection.