In this study, we have established the molecular basis of xeroderma pigmentosum (XP) in two unrelated Chinese families. In the first patient with consanguineous parents, we mapped the disease-causing locus XPC using single-nucleotide polymorphism microarray. Mutational analysis of the XPC gene showed that the patient is homozygous for a nonsense mutation, E149X. After developing DNA-based diagnosis of XPC, we screened another XP patient for XPC mutations. We found that the second patient is a compound heterozygote of 1209delG and Q554X in this gene. These are the first XPC-causing mutations identified in Chinese patients.