Tumors are not homogenous in nature, but are heterogeneous populations of cells. One population, the cancer stem cell (CSC), is thought to be responsible for the initiation and progression of the disease as well as contain inherent properties that make it more resistant to modern therapies. One of the key regulatory genes in these cells may be the oncogenic transcription factor c-Myc. We propose to study the regulatory and functional role c-Myc has in the Ewing’s sarcoma cancer stem cells (ESSCs) to increase our understanding of the genetic and molecular landscape of these cells. These studies can enhance our insights into the mechanisms of tumor initiation, therapeutic resistance, reoccurrence and metastasis.