Human epidermal growth factor receptor 2 (HER2/neu) gene amplification and HER2 protein overexpression have been associated with clinicopathological parameters and clinical outcome in many carcinomas. The aim of this study was to evaluate the frequency and prognostic impact of HER2 protein overexpression and gene amplification in small intestinal carcinoma (SIC). We performed immunohistochemistry (IHC) for HER2 protein and silver in situ hybridization for the HER2 gene in a total of 194 SICs. A total of 184 cases (94.8 %) were IHC 0 and 6 cases (3.1 %) were IHC 1+ with no gene amplification. HER2 protein overexpression (IHC 3+) with concordant gene amplification was detected in four cases (2.1 %), using the American Society of Clinical Oncology-College of American Pathologists guidelines for breast cancer. HER2 gene amplification was observed in an equivocal (IHC 2+) metastatic tumor in lymph node. No significant correlation was observed between HER2 status and clinicopathological parameters. Although HER2 protein overexpression and amplification were rare and did not correlate with clinicopathological parameters, further studies will be necessary to answer the question as to whether adjuvant therapy targeting the HER2 receptor might improve outcome in patients with a SIC with HER2 gene amplification and protein overexpression.