Background The purpose of this study is to describe human epidermal growth factor 2 (HER2) overexpression in head and neck squamous cell carcinoma (HNSCC) and re‐evaluate its potential as a target for HER2‐directed immunotherapies. Methods A retrospective cohort of patients with HNSCC receiving curative treatment was identified, and HER2 expression evaluated in archival tissue by immunohistochemistry and correlated with clinicopathological characteristics. HER2 expression data were also determined for HNSCC patients in The Cancer Genome Atlas. Results Nineteen percent of HNSCC and 39% of oropharyngeal HNSCC (OPSCC) were HER2 positive. HER2 expression positively correlated with nodal metastasis (p = 0.035). Patients with HER2‐positive tumors had decreased overall survival (p = 0.012), including within the human papilloma virus‐positive OPSCC subgroup (p = 0.007). Conclusions A substantial fraction of HNSCC overexpresses HER2 protein, suggesting it may be a suitable target for antigen‐directed immunotherapy. HER2 expression and its correlation with survival vary across HNSCC subsites, making it unsuitable as a prognostic marker.