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Angiosarcoma is a rare vascular malignancy, and there are few published data to guide chemotherapy treatment decisions. We present a retrospective analysis of angiosarcoma encompassing all anatomic sites of disease presenting to a single institution over a 14-year period. Characteristics at presentation and prognostic factors are reviewed. For patients with unresectable disease, progression-free survival with various chemotherapy regimens is described.Pathological confirmation of all cases was performed before they were included in this analysis. One hundred twenty-five patients with angiosarcoma were seen and treated between January 1, 1990 and December 31, 2003.Angiosarcoma showed marked variation by anatomic site regarding gender ratio, median age at diagnosis, overall survival, and response to chemotherapy. Overall 5-year survival was 31% for angiosarcoma. Superficial depth and negative microscopic surgical margins correlated with longer overall survival, but tumor size did not reach significance as a prognostic factor. For unresectable angiosarcoma, doxorubicin-based regimens yielded progression-free survival of 3.7–5.4 months. Paclitaxel achieved a progression-free survival of 6.8 months for scalp angiosarcoma and 2.8 months for sites below the clavicle.Angiosarcoma is an aggressive malignancy characterized by biologic heterogeneity at different anatomic sites and relative sensitivity to paclitaxel and doxorubicin.