Introduction: Oral Squamous Cell Carcinoma (OSCC) is one of the most prevalent cancers of oral cavity worldwide. The main components consisting basal lamina are collagen type IV and adhesive glycoprotein lamina. Local loss of basement membrane leads to formation of laminin-5, gamma-2 (laminin– 5γ 2) through proteolysis of basement membrane or synthesis in cytoplasm of neoplastic cells. Laminin– 5γ 2 is a protein that plays a central role in migration of the neoplastic cells during tumor invasion. Expression of this protein in cells and stroma adjacent to tumor can confirm the cellular invasion. The aim of this study was to evaluate expression of laminin– 5γ 2 in OSCC, verrucous carcinoma (VC), and dysplastic mucosa (DM), compared to normal mucosa (NM). Materials and Methods: 57, 31, 9, 9, and 8 paraffin blocks of squamous cell, OSCC, VC, DM, and NM (as control group) were scored as laminin-5γ 2 markers, respectively. The 10 and 40-fold magnifications were used to determine the percentage of colored cells. All the data were statistically analyzed by Chi-square and Mann-Whitney tests using SPSS version 20. Results: the findings demonstrated that expression of laminin marker was positive in the epithelium of 61. 3, 33. 3, and 22. 2% of the SCC, VC, and DM samples, respectively. On the other hand, it was negative in 100% of the NM samples. The distribution frequency of negative and positive laminin samples was assessed based on the type of lesions. The significance level was considered as 0. 006, which is less than 0. 05. There was a significant difference concerning the number of laminin positive lesions between the types of oral malignancies and normal mucosa. The SCC lesions revealed the highest positive results. Conclusion: According to the results of this study, laminin– 5γ 2 expression in the basement membrane, extracellular matrix, and epithelium of malignant tumor tissue might indicate the invasive and metastatic behavior of the OSCC.