Loss of heterozygosity indicative of the presence of tumor suppressor genes on chromosome 3p is commonly observed in carcinomas of various tissues. We have examined loss of heterozygosity on chromosome 3p in 27 oral squamous cell carcinomas using 15 highly informative microsatellite polymorphisms and constructed a deletion map of chromosome 3p. Overall, loss of heterozygosity at one or more loci was observed in 14 tumors (approximately 52%). A majority of these tumors (86%) show loss in more than one area. Three distinct regions were identified: 3p13-3p21.1, 3p21.3-3p23, and 3p25. These data suggest a role for at least three tumor suppressor genes on chromosome 3p in oral squamous carcinomas. The regions of deletions overlap with those described for carcinomas of other tissues and parallel those observed in lung carcinomas. This may reflect the common etiology of the two cancers.