Publisher Summary The human epidermal growth factor receptor (HER)-2/neu gene is a protooncogene located on chromosome. Overexpression of the HER-2 protein product is closely related to gene amplification in breast cancer. Many authors have reported that the amplification or overexpression of HER-2 in breast cancer is correlated with time to relapse and overall survival. To select breast cancers that are likely to be responsive to the therapy, it is necessary to evaluate HER-2 abnormalities. Two techniques that estimates protein overexpression and gene amplification are immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH). Although IHC and FISH have been approved by the United States Food and Drug Administration (FDA) as clinical tests for breast carcinoma, the question remains as to which is the better method of assessing the HER-2 status of patients with this disease. These two methods are discussed in detail in the chapter.