Method: An 82-year-old woman who had undergone conservative surgery and radiotherapy for breast cancer 10 years ago presented with multiple red-purplish papules on the skin of her right breast. Excisional biopsy followed by simple mastectomy was performed. Results: Excisional biopsy revealed a neoplasm composed of highly pleomorphic cells with prominent nucleoli forming solid areas and neoplastic slit-like vascular channels. Many mitotic figures and some individual apoptotic cells were also present. The tumor cells were positive for endotelial cell markers (factor VIII, CD31, CD34) and negative for CK7. The gross inspection of the mastectomy specimen showed multiple reddish-purple papule-like lesions on the skin, spreaded in an area of 12×10 cm. Sectioning showed numerous homogenous slightly hemorrhagic white nodules measuring from 2 to 12 mm located in the dermis. Histopatology and immunohistochemistry findings were consistent to those of the excisional biopsy. Infiltration of the subdermis was noted. Conclusion: Diagnosis was high grade post-irradiation angiosarcoma. Simple mastectomy is the treatment of choice. Adjuvant chemotherapy should be considered in high grade neoplasms like this one.