BACKGROUND Cell cycle arrest and increased cell proliferation have been demonstrated in oral lichen planus (OLP). This study evaluated the expression of cdk4, cdk6 and p16, important proteins in the G1 phase, in OLP and compared the expression of these proteins of OLP with those of normal mucosa. METHODS Expression of cdk4, cdk6 and p16 were investigated in 23 OLP and 10 normal mucosae using immunohistochemistry technique. Positive cells were counted and presented as a percentage of positive cells. RESULTS Expression of cdk4, cdk6 and p16 was observed in 3/10 (30%), 1/10 (10%) and none of normal mucosa, respectively. Expression of cdk4, cdk6 and p16 was detected in 18/23 (78.3%), 8/23 (34.8%) and 15/23 (65.2%), of OLP, respectively. The numbers of cdk4 and p16 positive cases of OLP were significantly higher than normal mucosa. In normal mucosa, the averages of the percentage of positive cells for cdk4 and cdk6 staining were 1.48 and 0.18, respectively. In OLP, the averages of the percentage of positive cells for cdk4, cdk6 and p16 staining were 2.73, 1.06 and 2.24, respectively. The percentage of cdk4-positive cells of OLP was significantly higher than those of normal mucosa group. CONCLUSION Oral lichen planus demonstrated overexpression of cdk4 and p16, but not cdk6, suggesting that epithelial cells in OLP are in the hyperproliferative state and in cell arrest. Altered expression of cdk4 and p16 provides evidence of the malignant potential in OLP.