Background: HER2 expression in the primary tumor and its lymph node metastases vary in gastric cancer,reflecting intratumoral heterogeneity. This finding also suggests that proliferation of a different clone in metastaticnodes is possible. In the current study, we aimed to determine the cause of discordance in HER-2 expressionin the primary tumor and lymph node metastases for patients with gastric cancer. Materials and Methods:Eighty-one patients with gastric cancer who had undergone radical gastrectomy and were found to have lymphnode metastasis upon pathological examination were included. Histopathological samples were obtained frombiopsies obtained during patient gastrectomies and lymph node dissection. HER2 status was evaluated by bothimmunohistochemistry (IHC) and silver in situ hybridization (SISH). Results: Sixty-four (79%) patients wereSISH (-), while 17 (21%) were SISH (+) in the primary tumor. However, in metastatic lymph nodes, HER2 statuswas SISH positive in 5 (28.3%) of the 64 SISH (-) primary tumor specimens. One of the 17 SISH (+) primarytumors was SISH (-) in the metastatic lymph nodes. Thus, SISH results for HER2 in both primary tumors andlymph node metastases were comparable, showing a concordance of 92.5%. In total, six patients demonstrateddiscordance between the primary tumor and lymph node metastases. The prevalence of HER2 discordance wassignificantly higher for patients in the pN2 and N3 stages (p=0.007). Although discordant patients had worsesurvival rates than concordant patients, the differences were not significant (p>0.05). Conclusions: Our studyindicates that the frequency of concordance in HER2 status, as determined by IHC or SISH, is high in primarytumors and their corresponding lymph node metastases for patients with gastric cancer. If there is a discrepancyin HER2 status, its evaluation by both IHC and SISH may be useful for detecting patients who would benefitfrom trastuzumab, and it would therefore help guide decision-making processes in administering treatment.