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We report the case of a young, 36-year-old patient diagnosed with multifocal breast carcinoma, undergoing neoadjuvant chemotherapy, surgery and adjuvant treatment. The patient presented an early recovery of liver disease after only 7 months of free interval. Histological reevaluation after liver biopsy revealed a HER2-positive disease, for which it was treated with first line chemotherapy including double anti-HER2 block. After 3 cycles the disease progressed at liver and encephalic level. It was therefore decided to treat brain localizations with whole-brain radiotherapy and to start a second line with capecitabine associated with lapatinib. This chemo-radiotherapy approach allowed to control the disease for 8 months. Following further progression (lymph node and bone), a third line was chosen with trastuzumab emtansine (TDM1). The encephalic disease remained stable for another 8 months, when due to visceral progression and worsening of clinical picture, TDM1 was interrupted and supportive therapies were started (Oncology). .