Patients with neurofibromatosis type I and breast cancer represent a subset of people who may be considered at high risk for secondary cancers after conventional whole breast radiation therapy and breast conservation surgery. A case of a 49-year-old woman with neurofibromatosis type I is presented. She was diagnosed with a 1.1-cm right breast infiltrating ductal carcinoma. Clinical, diagnostic imaging, and pathologic features are discussed. Her initial treatment plan of breast conserving therapy was thwarted when her sentinel node biopsy was positive for micrometastatic disease in 1/14 lymph nodes. She elected to have a bilateral simple mastectomy. This case addresses the rare dilemma of offering breast conservation therapy as a viable option for patients with neurofibromatosis type I. Current data on radiation-induced secondary cancers such as sarcoma after treatment for breast and other cancers are reviewed.