Wilms tumor is an embryonic neoplasm characterized by a large variation in histologic patterns. Cytogenetic investigations have identified nonrandom chromosomal changes characteristic for this tumor type, of which numerical changes, mostly trisomies for chromosomes 7, 8, and 12, are particularly frequent. Despite the abundance of cytogenetic information, with more than 350 published karyotypes, very little is known about the mode of karyotypic evolution. In this investigation, we have used 355 karyotypes of Wilms tumor to identify frequent imbalances. The most frequent were +1q, +6, +7q, +8, +12, +13, -11, and -16. Tumor cases were then classified with respect to the presence or absence of these imbalances and statistically analyzed to assess the order of appearance of chromosomal imbalances, as well as possible karyotypic pathways. We show that Wilms tumors develop through one major mode of karyotypic evolution, common to both low- and high-complex tumors, and that polyploid cases are relatively rare. We also establish a temporal order by which the different imbalances occur and show that at least two cytogenetic pathways exist, one dominated by gains and another by losses. We also show that these pathways are well separated and do not share a common set of late imbalances.