Her-2 status determination is an essential prerequisite before considering patient eligibility for treatment with trastuzumab. Currently the most common techniques to assess Her-2 status in routine practice are immunohistochemistry (IHC) and dual color FISH for receptor expression and gene amplification analysis, respectively. Despite both methods are well-established in breast cancer there are a variety of yet unsolved questions: 1. Do we really need IHC since interlab variation is still quite high (up to 30%)? 2. Are FISH and CISH equivalent techniques? 3. Are there any precautions to be taken if Her-2 is tested in non-breast cancer samples? 4. What is the value of Her-2 status in blood serum (ELISA)? 5. Do we get better response prediction if new Her2 antibodies, other techniques such as quantitative (q) RT-PCR or multiparameter assays according to downstream signalling pathways are applied? 6. Is Her-2 status still predictive when other therapeutic antibodies than trastuzumab (e. g. pertuzumab) or kinase inhibitors (e. g. lapatinib) are used? These questions will be discussed under the review of the recent literature and under own experiences obtained either by centralized Her-2 assessment in a variety of breast and non-breast cancer therapy studies and within international ring studies between reference labs from Australia (M. Bilous), Canada (W. Hanna), France (F. Penault-Llorcoa), Great Britain (M. Dowsett), Japan (R. Y. Osamura), and Netherlands (M. v. d. Vijver) in which we participated.