OBJECTIVE To investigate whether telomerase is reactivated in soft tissue tumor and whether telomerase activity is regulated at the transcriptional level. METHODS Fresh tissue samples of 24 soft tissue sarcomas were analyzed for telomerase activity by a radioactive polymerase chain reaction-based telomeric repeat amplification protocol assay and for human telomerase RNA (hTR) by an in situ hybridization assay. METHODS Tertiary care teaching hospital. METHODS Twenty-four patients with soft tissue tumor were surgically treated. Twelve patients had malignant fibrous histiocytoma, 5 had liposarcoma, 6 had leiomyosarcoma, and 1 had rhabdomyosarcoma. RESULTS Telomerase activity was detected in 4 sarcoma samples (17%), all of which were positive for hTR. Expression of hTR was demonstrated in 13 sarcomas (54%), 4 of which were positive for telomerase and 9 of which were negative for telomerase. One (50%) of 2 grade 1 tumors, 9 (50%) of 18 grade 2 tumors, and 3 (75%) of 4 grade 3 tumors showed hTR expression. CONCLUSIONS The relatively low frequency of telomerase activity in soft tissue sarcomas suggests that telomerase may not play an important role in tumorigenesis in these tumors. Telomerase ladders were demonstrated only in association with tumors expressing hTR. It is noteworthy that half of the patients with grade 1 and 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.