The multiple occurrence of squamous cell carcinoma is frequent in the upper aerodigestive tract (UADT). Risk factors not only for esophageal cancer, but also for multiple cancer in the UADT, were reviewed. Both cigarettes smoking and alcohol drinking are will known risk factors for esophageal cancer. The joint effect of these 2 factors on the occurrence of esophageal cancer is considered to be synergetic, but familial aggregation of esophageal cancer is also reported. Regarding the multiple occurrence of cancer of the UADT, both heavy smoking and heavy drinking play an important role. In addition, our studies revealed that a family history of UADT cancer might also be a risk factor for multiple cancer. Recent improvement of molecular biology techniques have helped to show that tumor-suppressor genes, such as p53 and FHIT, may be candidates for target genes of these risk factors.