Hungary is the leader both in oral cancer morbidity and mortality among the European countries. Oral cancer mortality had increased dramatically in Hungary to near fourfold between 1975 and 2002 both among the male and female populations. The increased oral cancer morbidity among the non-smoker, non-drinker elderly women and young adults, suggest that factors other than tobacco and alcohol consumption may also have important role in the pathogenesis of oral cancer. To reveal the epidemiological changes oral cancer cases and tumor-free controls were studied in the Department of Oral and Maxillofacial Surgery of the Semmelweis University in two phases between 1985-1986 and 2004-2005. In the 1st phase of the study, 460 cases with histologically confirmed oral squamous cell cancer and 350 tumor-free control cases were included. In the 2nd phase data of 550 oral cancer cases and 450 tumor-free controls were examined. Location of the tumors, alcohol consumption, and smoking habits of the male and female patients were separately evaluated. Among the oral cancer cases and their controls the ratio of smokers showed a significantly decreasing tendency in the examined period. Both the male oral cancer patients and their controls showed a significant decrease in the ratio of regular drinkers, whereas among the female tumor cases and controls the ratio of alcohol consumers were similarly low in both phases. The high male to female ratio of oral cancer cases significantly decreased over the examined period. Among elderly women (>60 yrs) oral cancer morbidity conspicuously increased. Among male cases the primacy of lower lip cancer had been taken over by sublingual cancer during the examined period. Among female patients, gingival tumor location was the most frequent in both phases. Our data suggest that the extraordinarily rapid increase in oral cancer morbidity and mortality in Hungary is not reasonable simply on the basis of excessive tobacco and alcohol consumption habits. Changes in the male to female ratio of oral cancer after 20 years, the older age of female patients as compared with males and the gender related difference of the prevalent tumor sites suggest some role of gender specific, systemic risk factors for oral cancer.