Squamous cell carcinoma (SCC) is the most common neoplasm of the oral cavity. It is aggressive, highly proliferative, and metastatic. This study aimed to evaluate the effect of LLLT and imiquimod on DMBA chemically induced lesions on the oral mucosa of hamsters. SCCs were induced on 25 hamsters. Animals of G1 (control 1) were killed and the presence of tumors confirmed; G2 (control 2) suffered no interventions for additional 4 weeks; animals of G3 (laser treatment) were irradiated (λ660 nm, 50 mW, CW, Ø=3 mm, 0.07 cm(2), 714.2 mW/cm(2), 133 s, 95 J/cm(2), 6.65 J) at every other day for 4 weeks; animals of G4 (imiquimod treatment) received 5 % imiquimod three times a week for 4 weeks; and animals of G5 (imiquimod and laser treatment) received both treatments for the same period. Samples were taken and underwent histological analysis by light microscopy and were investigated using immunohistochemistry for S-100(+) dendritic cells. In G1, G2, and G3, the evaluations showed malignant tumors and the absence of S-100(+) dendritic cells in the tumor stroma. In G4, 60 % of the animals had no malignant tumors, and S-100(+) dendritic cells were present in the stroma of the tumors as well as dysplasia. In G5, 40 % of the animals presented SCC, with scarce or no S-100(+) dendritic cells. The imiquimod treatment played a direct effect on SCC, demonstrated by the increased number of S-100(+) dendritic cells, which could suggest an important role of immune surveillance against neoplastic proliferation. Furthermore, its association with laser needs to be further investigated.