We have demonstrated previously a loss of constitutional heterozygosity on the short arm of chromosome 3 in approximately 50% of oral squamous cell carcinomas. In the present study, we have investigated 30 oral dysplastic lesions (DLs), presenting clinically as either erythroplakias or leukoplakias with histopathological features of either severe epithelial dysplasia or carcinoma in situ, for LOH on chromosome 3p using 15 microsatellite markers. Thirteen of the 30 LDs (approximately 43%) showed allelic imbalance at one or more loci. The pattern of loss in these lesions defined three noncontiguous regions of interstitial deletions that overlap with those defined for oral squamous cell carcinomas. These data indicate that the alteration of tumor suppressor genes on chromosome 3p is probably an early event in oral carcinogenesis. Additionally, 7 of the 30 DLs showed microsatellite instability. However, the frequency of loci showing microsatellite instability per lesion was low.