Introduction: HER2/neu is a protooncogene and its overexpression is associated with many malignancies, including oral cancers. It seems that confirmation or refutation of this association needs further studies. This study investigated a possible connection between HER2/neu overexpression and oral squamous cell carcinoma (OSCC).Materials& Methods: Immunohistochemistry (IHC) was employed in this descriptive-analytical study to detect HER2/neu expression in normal oral mucosa (NL, n=18), oral precancerous lesions of epithelial dysplasia (ED, n=7) and OSCC (n=12) within 8 months.Data were analyzed with descriptive statistics and Kruskal-Wallis and Fisher’s tests (a=0.05).Results: The three groups were matched in terms of their participants’ age and sex (p value< 0.05). HER2/neu immunoreactivity was of grades 0, 1+, 2+and 3+in 8 (44.4%), 1 (5.6%), 4 (22.2%), and 5 (27.8%) cases in the NL group, respectively.The corresponding results were observed in 3 (42.9%), 1 (14.3%), 3 (42.9%), and 0 (0%) cases in the ED group, and in 8 (66.7%), 2 (16.7%), 1 (8.3%), and 1 (8.3%) patients in the OSCC group, respectively. No significant differences were found in two-by-two comparisons between the NL and ED groups (p value= 0.55), between the NL and OSCC groups (p value=0.12), and between the ED and OSCC groups (p value=0.31) in the expression of HER2/neu.Conclusion: The findings of the present work suggested no significant association between HER2/neu expression and OSCC.