HER2-positive status is the sole criterion for identifying patients with breast cancer for Herceptin (trastuzumab) therapy. Accurate assessment of HER2 status is essential to ensure that all patients who may benefit from Herceptin are correctly identified. There are several assays available to determine HER2 status: the most common in routine clinical practice are immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). The pros and cons of those two tests and the other upcoming methods for assessing HER2 status (with a focus on chromogenic in situ hybridization CISH recently approved by European Commission) are described in this manuscript. The importance of adhesion to quality assurance programs is underlined. Finally, the different national testing guidelines are discussed.