Pheochromocytomas (PCCs) are rare catecholamine-producing tumors of the adrenal gland which may also occur elsewhere in the abdomen and are then called paragangliomas. A proportion of PCCs occurs in hereditary cancer syndromes, including multiple endocrine neoplasia Type 2 (MEN2), caused by mutations in the RET proto-oncogene, von Hippel-Lindau (VHL) disease, caused by VHL gene abnormalities, and the pheochromocytoma-paraganglioma (PCC-PGL) syndrome, caused by mutations in SDHB and SDHD. Since a proportion of PCCs occurs in children we hypothesized that germline mutations in RET, VHL, succinate dehydrogenase subunit B (SDHB), and subunit D (SDHD) occur more frequently in the pediatric age range. From our single-institution collection of PCCs, we have selected 10 cases that occurred in individuals up to 18 years of age at diagnosis. In these, we have performed mutation analysis on normal and tumor tissues for exons 10, 11, and 16 of RET and for the entire coding sequence of VHL, SDHB, and SDHD. The 10 patients include 7 boys and 3 girls, with an average age of 15.5 years (range 9-18 years). Two patients had germline RET exon 11 mutations (C634R) and 1 patient had an R64P germline mutation in the VHL gene. In the remaining 7 patients there was one patient from a family fulfilling the clinical criteria for VHL disease. All tumors were benign (average follow-up: 12 years) and were located in the adrenal. From our findings we conclude that (a) a large proportion (40%) of pediatric PCC patients is diagnosed in the context of inherited cancer syndromes, and (b) candidate gene analysis appears to be indicated to detect germline mutations.