Recent molecular evidence suggests that allelic deletions of chromosomes are involved in the carcinogenesis of various neoplasms, including oral squamous cell carcinoma (OSCC). To determine the role of 3p deletions in Japanese OSCC and to define the localization of putative tumor suppressor genes, we initially examined loss of heterozygosity (LOH), using nine microsatellite markers in 36 OSCCs and 28 oral epithelial dysplastic lesions (OEDLs). LOH on chromosome 3p was observed at one or more loci in 72% of OSCCs and 18% of OEDLs. Fourteen (61%) of 23 OSCC patients informative at D3S2450 (3pter-p24.2) showed LOH most frequently, in contrast to OEDL, where LOH was never seen at this locus. Interestingly, we found a significant association between an allelic deletion at this locus and the histologic grade of mode of tumor invasion. Therefore, we also examined allelic deletion on chromosome 3p telomeric to where D3S2450 was located. A common deletion region was identified between D3S2450 and D3S3591. Our results provide evidence for the presence of a tumor suppressor gene in a 0.8-cM region bordered by D3S2450 and D3S3591 at 3p25-p26, which may play a role in carcinogenesis and invasion of OSCC.