Immunohistochemical analysis shows strong staining of hypoxia-inducible factor-1α (HIF-1α) and the angiogenic factor, vascular endothelial growth factor in a malignant sporadic pheochromocytoma caused by a germline missense mutation in the SDHB gene [13], suggesting that activation of the hypoxia-response pathway may be a common theme underlying SDH (and also FH) mutation [14,15]. This evidence concerns the gene SDHB and hereditary pheochromocytoma-paraganglioma.