In oral squamous cell carcinomas of the head and neck, Laminin-5 gamma2 has been associated with tissue invasion, lymph node metastasis and histopathological grading. In the present study, we compared the expression of the subunit gamma2 of Laminin-5 under normal, dysplastic and invading epithelia in 65 biopsies previously diagnosed for oral squamous cell carcinoma. The number of gamma2-positive cells were analyzed in relation to patients' survival, tumor grading, size of the lesion, TNM stage, histopathological pattern of invasion and inflammatory reaction. Biopsies of oral squamous cell carcinomas were deparaffinised, processed for antigen unmasking procedures and stained with antibody anti-Laminin-5 gamma2. By light microscopy, 4 optical fields of x200 were selected in three different areas including normal, dysplastic and invading epithelia. Positive cells were counted and divided into three categories, which included <20 cells, between 21 and 50 cells and >50 stained cells. Patient survival was analyzed by Kaplan-Mayer curves. gamma2-positive cells were found in the basal layer of dysplastic epithelium, within inflammatory infiltrate, at the margins of differentiated invading islands and at the forefront of undifferentiated invading nests. Observations showed that an increased number of gamma2-positive cells correlated significantly with a shorter life expectancy under invading epithelia (log-rank test p<0.05), not when a count was performed under normal or dysplastic epithelia of the same patient. The number of gamma2-positive cells also correlated with the histopathological pattern of invasion. Our results show that gamma2 may be a reliable prognostic tool for oral squamous cell carcinomas.