FHIT, a candidate tumor suppressor gene, contains the FRA3B common fragile site and is highly susceptible to carcinogen damage. The pattern of mutational inactivation seen with the FHIT gene is unique compared with other known tumor suppressors. FHIT gene structure and expression have been shown to be altered in esophageal, head, neck, lung, gastric, breast, and cervical carcinomas. It has been demonstrated that FHIT exon loss is associated with smoking duration or asbestos exposure. The FHIT protein is a member of the histidine triad (HIT) superfamily and functions as a dinucleoside 5',5'''-P1,P3-triphosphate hydrolase.