Wilms tumor (WT), a sporadic and familial childhood kidney tumor, is genetically heterogeneous. One WT gene, WT1 at 11p13, has been cloned, but only a minority of WTs carry detectable mutations at that locus. WT1 can also be excluded as the predisposition gene in most WT families, implying the existence of other WT genes. Studies of WT families have demonstrated that familial predisposition is also heterogeneous and involves at least two other loci besides WT1. In addition to WT1 and the familial predisposition genes, a role for other genes in the development of WTs is implied by the somatic occurrence of genetic and epigenetic alterations such as loss of heterozygosity and loss of imprinting in tumors and, rarely, the observation of nonchromosome‐11 constitutional aberrations in WT patients. Determining the pattern of presence or absence of these various genetic alterations in tumors and elucidating the function of the genes involved will provide a better understanding of the cellular processes that are critical for normal cell growth and differentiation, but are abrogated in the course of tumorigenesis. Am. J. Med. Genet. 79:260–267, 1998. © 1998 Wiley‐Liss, Inc.