Previous human stem cell-based models of neuroblastoma utilized protocols to differentiate human pluripotent stem cells to NCCs.18,19 However, these protocols lacked caudalizing factors (e.g., retinoic acid), and resulting NCCs show high expression of ETS1, a marker of cranial NCCs.21,29 Although neuroblastoma is believed to arise from tNCCs and not cranial NCCs, mis-expression of MYCN in NCCs generated by the early protocols produced tumors that shared features of neuroblastoma. This evidence concerns the gene MYCN and neuroblastoma.