Abnormal expression of cell cycle regulatory proteins, particularly cyclin D1, has been implicated in the pathogenesis of several types of cancer. We have examined the expression of cyclin D1 in histological sections of oral squamous cell carcinomas (SCCs) using anti-cyclin D1 antibodies with an immunoperoxidase technique. Cyclin D1 nuclear staining was observed in 73 of 88 (83%) cases of oral SCC. In 54 of these 73 (74%) cases, positive cyclin D1 staining was also found in the normal appearing epithelium immediately adjacent to the cyclin D1-positive SCCs. No significant correlation was found between the expression of cyclin D1 and the patients' age, sex, oral habits, cancer location and STNM status. The Kaplan-Meier analysis showed that patients with tumors containing more than 10% cyclin D1-positive cells had significantly shorter overall survival than those with tumors containing less than 10% cyclin D1-positive cells or with cyclin D1-negative tumors (P<0.05). Patients with positive lymph node status also had significantly shorter overall survival (P<0.01). These results indicate that cyclin D1 may play an important role in the genesis of oral SCC and may serve as an adjuvant marker of worse prognosis in patients with oral SCCs in Taiwan.