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Silver in-situ hybridization (SISH) is an automated technique that can be used for assessment of HER-2 gene in patients with breast cancer. It is a rapid, reliable, and reproducible technique that allows interpretation using bright field with retaining of the architecture. The aim of this study is to analyze HER-2 state in breast carcinoma cases using immunohistochemistry (IHC) and SISH, with validation of some cases by fluorescence in-situ hybridization (FISH).We retrospectively analyze the HER-2 gene status in 201 cases diagnosed as invasive breast carcinoma in the National Cancer Institute, Cairo University, using IHC and SISH. We adopt the lastly updated American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines, 2013. Automated immunohistochemistry and SISH were done using Ventana Benchmark XT system using whole tumor section. Nineteen cases were also tested by FISH.Of 201 cases, 25 were positive (score 3+) by IHC and the remaining cases (176 cases) were equivocal by IHC (score 2+), from which 40 cases turned to be amplified after testing by SISH, and the rest were confirmed to be nonamplified by SISH. To validate the results, FISH was also performed upon 19 equivocal cases, where two cases were amplified (both were also amplified by SISH) and 17 cases were nonamplified (all were nonamplified by SISH also), highlighting very high degree of concordance between SISH and FISH. Five cases were discovered through SISH to have chromosome 17 polysomy and proved to be nonamplified.SISH is a good comparable test to FISH in evaluation of HER-2 status in breast carcinoma. Both of them achieved high concordance rate, making any one of them the best adjunct test to validate HER-2 immunohistochemistry, aiming at proper selection of patients who are candidate for HER-2-targeted therapy.