Locally advanced breast cancer can lead to self-destruction, necrosis, and malodor, which may reduce the patients' quality of life. We encountered a case where the combination of Mohs' paste and systemic drug therapy for locally advanced breast cancer improved quality of life and achieved marked disease control. The patient, a woman in her 70s, was referred to our department with suspected right breast cancer. After thorough examination, she was diagnosed with cT4bN3aM1(PUL), cStage Ⅳ, invasive ductal carcinoma, HER2 type. Mohs' paste treatment began on the 8th day, and systemic drug therapy was initiated on the 22nd day. Mohs' paste was applied once a week for a total of 4 times, resulting in significant tumor shrinkage. More than 6 months have passed since the start of treatment, and a complete response has been maintained, including pulmonary metastasis. Mohs' paste is a useful treatment for locally advanced breast cancer with self-destruction and necrosis.