Neuroblastoma is a pediatric cancer of embryonic origin from neural crest cells. Neuroblastoma has a great medical and social impact because it is occurring with major frequency in pre-scholar age with metastatic disease showing less than 40% of survival at 5-years. In children, metastatic neuroblastoma has very few recurrent mutations but several chromosome structural copy variations. The tumorigenesis of neuroblastoma is still largely unknown; however recently, genomic wide association studies have shown that several gene allelic variants are associated with neuroblastoma predisposition. Many of these gene variants are related to maintaining the chromatin and mitosis integrity. In the present report, I suggest that neuroblastoma predisposing alleles may match by chance influencing the chromatin structure already during the early phases of embryonic life and inducing chromosome instability and structural damages.