Postradiation cutaneous angiosarcoma of the breast is a rare, delayed complication of adjuvant radiation treatment for breast carcinoma and is associated with a worse prognosis than the original primary cancer. Recent studies have characterized the diagnostic utility of MYC and NOTCH1 receptor expression as markers for secondary radiation-associated angiosarcomas. Herein, we report an exophytic secondary breast angiosarcoma with MYC and NOTCH1 immunoreactivity. This case illustrates the utility of these markers for the identification of radiation-associated angiosarcoma with MYC and NOTCH1 expression, potential for targeted therapy and need to identify patients for further studies of the clinicopathologic and prognostic significance.