In an effort to clarify the role of telomerase in the pathogenesis of pheochromocytomas and neuroblastomas, and to test whether its component could serve as a marker of malignancy, we measured telomerase reverse transcriptase (TERT) mRNA in 31 human pheochromocytoma tissue samples (5 malignant, 23 benign and 3 suspected malignant) and 16 neuroblastoma tissues (9 unfavorable and 7 favorable). All cases were classified by both the clinical course and histopathological examination. Malignancy was defined as the presence of metastasis and/or extensive local invasion. TERT mRNA was determined by nested PCR and a real-time PCR system (LightCycler). By nested PCR methods, 5 of the 5 malignant pheochromocytoma samples were positive (sensitivity = 100%), and 21 of 23 benign pheochromocytoma samples were negative (specificity = 91%) in pheochromocytomas. Four out of five malignant tumors were positive for either hTERT expression or Ki-67/MIB-1 immunoreactivity. In the neuroblastoma tissues, 9 of the 9 unfavorable samples were positive (sensitivity = 100%), and only 2 of 7 favorable samples were negative (specificity = 29%). We also determined the expression of the hTERT mRNA by real-time PCR to quantitate the mRNA. The mean values of hTERT mRNA by real time PCR in benign and malignant pheochromocytomas were 2 and 26 arbitrary units (AU), respectively. The difference was not significant by the U-test. The mean values of hTERT mRNA in favorable and unfavorable neuroblastoma were 203 and 497 AU, respectively. This difference was also not significant (U-test). N-Myc mRNA expression correlated with the expression of hTERT mRNA in the neuroblastoma samples (r = 0.534, p = 0.0317). Thus, hTERT mRNA might be a potential marker for estimating the malignancy of pheochromocytomas and neuroblastomas.