Cancer cells are derived from their precursor cells, which normally develop to the matured cells to form individual organs. Neuroblastoma, one of the most common pediatric solid tumors, originates from possible cancer stem cells derived from the neural crest. During the development, neural crest cells segregate into several lineages such as sensory, enteric and sympathetic neurons. However, the genetic events to cause neuroblastoma occur only in the sympathetic precursor cells or cancer stem cells. Furthermore, spontaneous regression of a subset of neuroblastoma found in patients under one year of age mimics a developmentally programmed neuronal cell death that occurs in normal sympathetic neurons during the perinatal period. Thus, the genetic events to cause neuroblastoma may be programmed to occur in a lineage-specific as well as developmentally regulated manner. In this review, we discuss about the molecular link between neural development and the genesis of neuroblastoma based on our comprehensive genomics approach.