The WT1 gene is a tumor suppressor gene for Wilms' tumor (WT). Inactivation of both alleles has been proposed as the cause of WT. We encountered a patient with Denys-Drash syndrome associated with WT whose WT1 gene had a homozygous point mutation not only in WT but also in renal tissue adjacent to the WT and in the germline. These findings indicate that factor(s) other than the loss of WT1 are required for WT to develop.