We report the clinical, morphological and molecular findings regarding a 37-year-old woman with breast cancer metastatic to the liver and describe the different expression of a tumor marker in the primary and secondary lesions and the singular responsiveness to treatment. The patient suffered from a carcinoma of the left breast with metastasis to the liver. High HER-2 protein expression assessed by immunohistochemistry and HER-2/neu amplification determined by FISH were present in the primary tumor, while the liver metastasis showed a lower value of HER-2 protein (2+) and absence of HER-2/neu amplification. The patient was treated with chemotherapy (epirubicin and paclitaxel) followed by trastuzumab and docetaxel. After 5 months, at the completion of chemo-immunotherapy, liver ultrasonography showed a further hepatic response. A second biopsy was performed on the residual liver nodule: immunohistochemistry revealed negative (1+) HER-2 expression and FISH confirmed that the HER-2/neu gene was not amplified. The different amplification of HER-2 and expression of its protein in primary and metastatic carcinoma could be important for planning adequate treatment.