Breast cancer is a well-known heterogeneous tumor, that includes inter- and intra-tumoral heterogeneity. These modifications in the phenotype can lead to modify the therapeutic strategy. The author reports the original case of a 66-year-old Caucasian woman, diagnosed with a breast cancer 18 years before. Initially it was a 32-mm, grade 2, ductal infiltrating breast carcinoma, negative for hormone receptors. The patient was treated with conservative surgery, and axillary dissection (eight positive nodes out of 21). Adjuvant chemotherapy and radiotherapy were delivered. Ten years later, the patient was diagnosed with pulmonary relapse. Biopsies were negative for hormone receptors and also for human epidermal growth factor 2 (Her2). The patient received chemotherapy. One year later, pleura effusion appeared. Biopsies of the pleura confirmed the metastasis of breast cancer, hormone receptors negative, but positive for Her2. She was then diagnosed with a paraneoplastic dermatomyositis. Eight lines of chemotherapy were given and currently the patient is continuing trastuzumab. That case illustrates the story of a very long-surviving breast cancer and its dedifferentiation. It underlies the necessity to realize new biopsies when the tumor relapses.