PHOX2B (Paired mesoderm homeobox protein 2B) is an essential transcription factor determinant of neuronal fate from neural crest precursors. Neural crest progenitors are a transient, migratory population of multipotent stem cells that develops into neurons of the sympathetic chain, neuroglia and chromaffin cells of the adrenal medulla during embryonic development. Mutations in PHOX2B have been associated with the development of disease such as congenital central hypoventilation syndrome, Hirschsprung disease and neuroblastoma.

Neuroblastoma is the most common malignant pediatric extra-cranial tumor of the sympathetic nervous system. It is a heterogenous group of tumors histologically ranging from undifferentiated or poorly differentiated neuroblasts to predominantly full differentiated neurons. Compared to normal tissues, PHOX2B was found overexpressed in neuroblastoma and cell lines. Often in undifferentiated and poorly differentiated neuroblastomas, immunohistochemistry is required to confirm neuroblastic lineage. IHC studies have demonstrated PHOX2B expression in all neuroblastoma, and have suggested that PHOX2B is a potential marker for diagnosing undifferentiated neuroblastoma. Supplemental studies containing a panel of antibodies can differentiate neuroblastoma from other small-blue-round cell tumors such as Ewing's sarcoma and Wilms' tumor.