Telomerase is an RNA-dependent DNA polymerase that synthesizes TTAGGG telomeric DNA onto chromosomal ends to compensate for sequence loss during replication. It has been detected in a variety of human malignancies, suggesting that such activity may play a role in the tumorigenic process. To determine whether telomerase is reactivated in malignant fibrous histiocytoma, 12 tissue samples with this tumor were analyzed for the telomerase activity by a radioactive PCR-based TRAP (telomeric repeat amplification protocol) assay. All of the tumors were further investigated for the expression of human telomerase RNA (hTR) by an in situ hybridization (ISH). Telomerase activity was detected in one (8.3%) sample. Expression of hTR was demonstrated in 7 (58.3%): one telomerase-positive and six telomerase-negatives. These data indicate that the reactivation of telomerase is an uncommon event and not an important factor involved in tumorigenesis in malignant fibrous histiocytoma. It is noteworthy that 50% of the patients with grade 2 tumors expressed hTR, suggesting that telomerase RNA may be useful as a marker for identifying tumor aggressiveness earlier than the conventional histopathologic grading scale.