Linkage studies of kindreds with the nevoid basal cell carcinoma syndrome and the high frequency of chromosome 9 allele loss in sporadic basal cell carcinomas indicate that chromosome 9 may contain tumor suppressor genes important in the development of sporadic and familial basal cell carcinomas. The recent mapping of the Ferguson-Smith syndrome, which predisposes affected individuals to the development of multiple lesions histologically indistinguishable from squamous cell carcinomas, suggests that tumor suppressor genes on 9q may also be important in the development of squamous cell neoplasms of the skin. Fifty-four non-melanoma skin cancers (24 basal cell carcinomas, 14 squamous cell carcinomas, and 16 cases of Bowen's disease) were examined for loss of heterozygosity on chromosome 9. Allelic loss at one or more loci on chromosome 9 was observed in 14 of 24 basal cell carcinomas, four of 14 squamous cell carcinomas, and three of 16 cases of Bowen's disease. Allelic deletion of one or more 9q markers was seen in 14 basal cell carcinomas, three squamous cell carcinomas, and three cases of Bowen's disease. Five basal cell carcinomas had interstitial deletions and in one the breakpoint mapped within the nevoid basal cell carcinoma syndrome locus. 9p loss occurred in three of nine informative squamous cell carcinomas. Allelic deletion of 9p markers was not seen in 19 basal cell carcinomas and seven cases of Bowen's disease. These findings suggest that chromosome 9 contains one or more tumor suppressor genes important in the development of both basal and squamous cell carcinomas of the skin.