Background: The evaluation of gene amplification and/or protein overexpression of HER2 in gastric cancer is a prerequisite to establish an adequate treatment strategy. Gastric tumors are heterogeneous and separate evaluations lead to uncertainties in localizing distinct clones and are time consuming. The aim of this study was to evaluate the feasibility of gene-protein platform in comparison to single staining methods. Methods: Immunohistochemistry (IHC) plus silver in situ hybridization (SISH) (IHC/SISH) and the new gene-protein platform (gene/protein) method for HER2 were performed in randomly collected 100 cases of gastric carcinoma. Evaluation was performed by two observers, in discrepant cases a third observer was consulted to make a decision by consensus. Results of IHC and SISH were compared with gene/protein staining. Rüschoff criteria were applied. Tumors showing HER2 expression 3+ or amplification were considered HER2 positive. Results: 96 of 100 samples were eligible. Amplification was observed in 14.6% by both, conventional SISH and gene/protein platform. 70.8% by IHC and gene/protein had no expression (0) and 10.4%/11.5% (IHC vs. gene/protein) had weak (1+) HER2 expression. Moderate expression (2+) was observed in 9.4% by IHC and 7.3% by gene/protein. Rate of overexpression (3+) was similar in IHC (9.4%) and gene/protein (10.4%). There were complete concordances (100%; κ=1) in IHC assessment of cases with score 0 and SISH amplified tumors. High concordance are shown in score 1+ (98.96%; κ=0.947) and 3+ (96.88%; κ=0.825) cases. Concordance in cases with score 2+ was found in 95.83% (κ=0.728) of the observations. After third observation, there were 5 discordant cases with most discrepancies in assessment of IHC score 2+ or 3+. Conclusions: Gene-protein platform has been tested for first time in gastric carcinoma. Results showed that this novel platform can be a feasible alternative to single methods. Discrepancies in cases with moderate HER2 expression are a result of observer variability.