Frequent allelic imbalances, including loss of heterozygosity (LOH) and microsatellite instability (MSI), have been found on the long arm of chromosome 2 (2q) in several types of human cancer. This study was designed to identify the tumor suppressor locus (or loci) associated with oral squamous cell carcinoma (SCC) on 2q. To better understand the details of genetic alterations on 2q, we performed polymerase chainreaction analysis of microsatellite polymorphisms corresponding to 10 loci on this chromosome. We identified a novel tumor suppressor locus in this region in primary oral SCCs. To further determine the role of 2q deletions in oral carcinogenesis, 19 oral SCCs (19 sets of primary and corresponding normal tissues) were examined for allelic imbalances (LOH or MSI) on 2q, using ten microsatellite markers. Among these 19 patients, 11 (57.9%) showed LOH at one or more loci. Deletion mapping of these tumors revealed four discrete, commonly deleted regions on the chromosome arm. Furthermore, we detected MSI in 4 of the patients (21.1 %).We compared our results with clinicopathologic features. A number of sites with LOH on 2q were detected in early stage lesions, and the frequency of LOH was slightly but not significantly higher in later clinical stages. Our results suggest that allelic imbalances on 2q are involved in the development of oral SCC and that one or more putative tumor suppressor genes contributing to the pathogenesis of this disease are present on 2q.