There are clear interfamilial differences in predisposition to pheochromocytoma in VHL disease. In a minority of families, pheochromocytoma is the most frequent complication of this disease but in other families, it is rare (Maher et al. 2011). VHL disease has been subclassified according to the presence (type 2) or absence (type 1) of pheochromocytoma. In most cases, pheochromocytoma-positive VHL families also have a high incidence of renal cancer (type 2B), but in some type 2 VHL disease families, pheochromocytoma is common and renal carcinoma is rare (type 2A). In addition, rare VHL missense mutations may cause a familial pheochromocytoma-only phenotype (type 2C) (Woodward et al. 1997). Up to 11 % of patients with apparently sporadic pheochromocytoma may have a germline VHL mutation (Neumann et al. 2002). Both adrenal and extra-adrenal pheochromocytomas can occur in VHL disease. Pheochromocytoma in VHL disease patients is usually associated with missense mutations, and although the overall risk of malignancy in pheochromocytomas is ~10 %, the rate in VHL disease appears to be lower (~5 %).