Objectives. To investigate the effect of systemic administration of the immunosuppressant dexamethasone (DM) while inducing hamster buccal pouch DMBA carcinogenesis. Materials and Methods. Two different experiments were performed. In the first experiment, hamsters’ right buccal pouches in group A (n = 10) were painted three times per week with 7,12-dimethylbenzanthracene (DMBA) 0.5%, while pouches of animals in group B (n = 4) were painted with mineral oil only. Two animals were sacrificed every three weeks to obtain histological samples and to evaluate pathological abnormalities. After 12 weeks of exposition and with no macroscopic evidence of neoplasms, dexamethasone DM (1 mg/kg) was administered daily for 7 days to the last two animals in the study. In the second experiment, DM was administered since DMBA exposition, following the same protocol as the first experiment. Results. The time of macroscopic neoplasm development was reduced when DM-DMBA coexposition was employed, finding tumors after 10–12 weeks of exposition. In addition, the frequency of histopathological lesions was higher. Conclusion. Immunomodulatory action of dexamethasone may reduce the time of oral squamous cell carcinoma (OSCC) induction and may increase the incidence of neoplasms developed.