Recent years have witnessed the exciting discovery of cancer stem cells (CSCs) in solid tumors. Similar to normal stem cells, CSCs can reproduce themselves through the process of self-renewal which can be studied in serial transplantation assays. Additionally, cancers derived from purified CSCs recapitulate the heterogeneous phenotypes of the parental cancer from which they were derived, reflecting the differentiation capacity of CSCs. Based on these stringent criteria, the Oekel lab has made major steps towards prospective isolation of novel CSCs in human Wilms’ tumor (WT), the most common pediatric renal malignancy, and has shown that these cells express developmental markers of embryonic renal stem cells. At the same time the Huff lab has been able to generate the first ever endogenous tumor mouse model for WT by engineering mice to carry the same genetic alterations observed in human WTs. The mouse tumors are histologically like human WTs and proteomic analysis of them has provided insight into signaling pathway activation in both mouse and human tumors.