HER2 gene amplification was explored using the silver stain hybridization in situ (SISH) technique in colon, prostate, lung, ovarian and breast carcinomas. Clinical pathological features and immunohistochemical (IHC) expression were evaluated for HER2 in 225 carcinomas. All cases were subjected to SISH investigation. Statistical analysis revealed an association between HER2 protein expression and gene amplification in breast carcinoma. 14% of colon carcinomas (5 IHC score 0, 1 score 1+ and 1 score 2+), 2% of prostate carcinoma (IHC 2+), 4% of lung carcinomas (IHC 2+) and 16% ovarian carcinomas (IHC 3+) revealed gene amplification. SISH is an advantageous technique for the detection of gene amplification. The use of the SISH technique in breast carcinoma may be an alternative to other in situ hybridization (ISH) techniques however more detailed studies seem necessary to detect HER2 gene amplification in other human malignancies.