HER-2 is overexpressed in 20 to 30% of breast cancer. Generally, metastases of a breast tumor have the same HER-2 status, although some discordances were reported.We report a case of reduction in HER-2 expression assessed by immunohistochemistry, following one day of a Trastuzumab injection, of a metastatic breast cancer to lymph nodes. Initially, the breast tumor HER-2 status was positive according to the same technique.We raise a hypothesis about technical interference and discuss the case in the framework of the existing literature.