PHOX2B (Paired-Like Homeobox 2B) is a transcriptionfactor encoded on chromosome 4p13 that is essential forthe development and maintenance of the autonomicnervous system. PHOX2B expression is normally restrictedto neural crest-derived cells committed to thenoradrenergic lineage, where it plays critical roles indifferentiation and neuronal specification. Becauseperipheral neuroblastic tumors arise from thesympathoadrenal lineage, PHOX2B is strongly expressed inneuroblastomas, ganglioneuroblastomas,ganglioneuromas, paragangliomas, andpheochromocytomas. Studies have shown that PHOX2B isnegative in most other small round blue cell tumors,making it a highly valuable research marker forneuroblastic differentiation and autonomic nervous systemtumor biology.