Li-Fraumeni syndrome (LFS) is an inherited autosomal-dominant tumor-predisposition disorder caused by germline mutations in the TP53 tumor suppressor gene. Since patients with LFS are likely to develop therapy-related cancers, radiation therapy should be avoided if breast cancer is found in these individuals. Herein, we present a case of secondary breast cancer in an LFS patient after radiation and chemotherapy for the first diagnosed breast sarcoma.