Background: Despite the available data on demographic information of oral squamous cell carcinoma (OSCC), the changing trend of histopathologic pattern of OSCC has not conducted yet, in Iran. The aim was to investigate the pattern of histopathologic features of OSCC in Iran by analyzing the patients referred to Cancer Institute, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran, during 2006-2015. Materials and Methods: The study was a retrospective institutional study. The pathology records with the diagnosis of OSCC were retrieved from Iran National Tumor Bank, Cancer Biology Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran, during 2006-2015. The demographic characteristics and histopathologic features were recorded and analyzed for possible trend. Descriptive analysis was used for statistical interpretation. Results: The data showed an increasing number of moderately and poorly differentiated OSCC. Accordingly, higher increasing rate in tumor size and vascular, perineural invasion was detected. Conclusion: On the basis of histopathologic features, moderately differentiated OSCC with increasing rate of tumor size and vascular, perineural invasion was indicated in recent decade. Based on the findings, lower differentiation potentially is compatible with worsen prognosis.