A childhood tumor—from the beginning Many adult cancers arise from clonal expansions of mutant cells in normal tissue. These premalignant expansions are defined by somatic mutations shared by the cancers. Whether pediatric cancers originate in a similar way is unknown. Coorens et al. studied Wilms tumor, a childhood kidney cancer. Phylogenetic analyses revealed large clones of mutant cells in histologically and functionally normal kidney tissue long before tumor development. Thus, like adult tumors, Wilms tumor appears to arise from a premalignant tissue bed. Science , this issue p. 1247