Angiosarcoma of the scalp is a rare but highly aggressive malignant tumor that differentiates toward vascular endothelial cells and shows a tendency for diffuse, often clinically occult spread. A 65- year-old Caucasian man presented with multiple erythematous skin lesions at the right scalp hemisphere and a prominent forehead edema that had developed during a period of 2 months. The clinical diagnosis of angiosarcoma was confirmed by histopathology. Because of the advanced local progression of the tumor and the unilateral localization on the right side of the scalp, we initiated an intra-arterial chemotherapy using pegylated liposomal doxorubicin (Caelyx) (8 mg/cycle every 4 weeks by an A. carotis externa port system). In addition, the patient received pegylated interferon alfa (50 μ g/wk) by a percutaneous intralesional injection route. After 2 months, the tumor showed a marked regression; after 4 months, only one nodule located at the margins of the area perfused by the A. carotis externa persisted but regressed after focal irradiation. At 30 months after diagnosis, the patient shows no recurrence of tumor growth. In combination with intralesional interferon alfa, intra- arterial doxorubicin may be a promising innovative therapeutic option for localized scalp angiosarcoma, a hitherto poorly manageable and aggressive malignant tumor. A 65-year-old Caucasian man presented with multiple erythematous skin lesions at the right scalp hemisphere and a prominent forehead edema that had developed during a period of 2 months. The clinical diagnosis of angiosarcoma was confirmed by the histopathology. Because of the advanced local progression of the tumor and the unilateral localization on the right side of the scalp, we initiated an intra- arterial chemotherapy using pegylated liposomal doxorubicin (Caelyx) (8 mg / cycle every 4 weeks by an A. carotis externa port system). In addition, the patient received pegylated interferon alfa (50 μg / wk) by a percutaneous intralesional injection route. After 2 months, the tumor showed a marked regression; after 4 months, only one nodule located at the margins of the area perfused by the A. carotis e At 30 months after diagnosis, the patient shows no recurrence of tumor growth. In combination with intralesional interferon alfa, intra-arterial doxorubicin may for a innovative therapeutic option for localized scalp angiosarcoma, a hitherto poorly manageable and aggressive malignant tumor.