Novel insights into the molecular pathogenesis of neuroblastoma (NB), a severe pediatric tumor originating from neural crest cells and accounting for 15% of childhood cancer mortality, have been gained after the identification of germline as well as somatically acquired mutations in the genes encoding the paired-like homeobox 2b (PHOX2B) transcription factor [1], [2] and the Anaplastic Lymphoma Kinase (ALK) tyrosine kinase receptor [3]. The gene discussed is PHOX2B; the disease is neuroblastoma.