Wilms tumors (WT) arise from abnormally proliferating metanephric blastema, and retain a high degree of dedifferentiation. Histologically, WT appear mostly triphasic with variable amounts of epithelial, blastemal and stromal components. In sporadic WT, of which several hundred have now been analyzed, WT1 mutations are present in less than 10% of cases. The WT1 gene encodes developmentally regulated transcription factor. The emporal and spatial distribution of WT1 during kidney development suggests a role for the protein in mediating mesenchyme differentiation. Hence, lack of the differentiating signal initiated by WT1 may be crucial for the genesis of WT that carry WT1 mutations. WT1 remains the only tumor suppressor gene directly implicated in the initiation of Wilms tumorigenesis. However, the linking of CTCF to loss of imprinting suggests that a search for mutations in this gene may implicate it in the etiology of loss of imprinting WT.