Allelic imbalance or loss of heterozygosity (LOH) and microsatellite instability (MSI) have been used to identify regions on chromosomes that may contain putative tumor suppressor genes. To obtain a detailed understanding of genetic alterations in oral cancer, 10 highly polymorphic markers mapped on chromosome 2 were used to examine 25 cases of oral squamous cell carcinoma (SCC). With these, we analyzed chromosome 2q for LOH in 25 primary oral SCCs and constructed a deletion map for this arm of the chromosome. LOH was detected in 16 (64%) of the 25 informative samples at one or more of the loci examined. MSI was observed in 5 (20%) of the 25 cases. Among the loci examined, LOHs were restricted to D2S1328 and D2S206 on chromosomes 2q14-21 and 2q36, respectively, with the former locus showing a rate of 5 (20.8%) and the latter a rate of 6 (25%) of the 24 informative cases. These observations taken in conjunction with data from 40 former cases analyzed at our laboratory suggest that the high incidence of LOH at chromosome 2q is associated with carcinogenesis of oral SCC. The regions that comprise the D2S1328 and D2S206 loci may play an important role in the development of oral SCC, perhaps containing sites that harbor a putative tumor suppressor gene.