INTRODUCTION: Oral squamous cell carcinoma (OSCC) is the commonest malignancy in oral cavity. Dysregulated inflammatory processes could impose a cancer risk. Cytokines are inflammatory mediators that can induce cell proliferation. Interleukin-10 is a pleiotropic cytokine which has a dual role in cancer pathogenesis. It contributes to tumor growth and in other cases to tumor rejection. OBJECTIVES: To evaluate and correlate the expression of IL-10 in different histopathological grades of OSCC, as well as to assess its serum and salivary levels. MATERIALS AND METHODS: Immunohistochemical (IHC) study using the IL-10 antibody was done on 20 surgical specimens and 5 normal mucosal tissues taken from OSCC patients and healthy individuals, respectively. Serum and salivary levels of IL-10 were also measured with a human IL-10 ELISA Kit in both patients and controls. RESULTS: OSCC biopsies showed immunoreactivity to IL-10, while normal tissues were immunonegative. The IHC staining intensity was directly proportional to the grading of OSCC. Conversely, it showed no significant correlation to the disease stage. The difference in the serum and salivary IL-10 levels in patients and controls was not statistically significant. However, there was a significant correlation between IL-10 tissue expression and its serum and salivary levels in OSCC patients. CONCLUSIONS: IL-10 is expressed in OSCC biopsies. Additionally, the levels of IL-10 in tissue, serum and saliva were correlated to each other. This could reflect the same way of regulation of IL-10 in different parts of the body.