The objective of the present study was to correlate the expression of cyclin D1 with the expression of p21 in 28 cases of oral squamous cell carcinoma (OSCC), as well as to compare the expression of both with a histological graduation of this neoplasm. Immunohistochemistry was used to obtain the expression of cyclin D1 and p21. The results of statistical analysis showed no correlation between the expression of cyclin D1 and p21. Also, there was no correlation between the mean numbers of cyclin D1 positive nuclei and p21 positive nuclei and the histological scores of malignancy. However, the marked expression of cyclin D1 in high-grade tumors supports its role in proliferative activity. In contrast, p21 seems unable to arrest tumor progression in OSCC.