The human homologue of Drosophila patched (PTCH), located at chromosome 9q22.3, was recently identified as a candidate tumor suppressor gene for familial and sporadic basal cell carcinomas. Squamous cell carcinomas (SCCs) of the skin display allelic loss in this chromosomal region, which, in addition to the PTCH gene, contains the DNA repair gene xeroderma pigmentosum complementation group A (XPA). Patients with xeroderma pigmentosum are predisposed to non-melanoma skin tumors because of deficient excision repair of ultraviolet-induced DNA damage. Mutation analysis by single-strand conformation analysis and direct DNA sequencing of all 23 exons of the PTCH gene and all six exons of the XPA gene in 14 SCCs did not reveal structural alterations in any of these genes. Additionally, analysis of PTCH expression by in situ hybridization in SCCs revealed no evidence of upregulation of PTCH mRNA, confirming the lack of mutations in this gene. These findings suggest that another, yet to be identified gene or genes on chromosome 9q are involved in SCC tumorigenesis.