Background: As the enzyme telomerase extends the life of the cell through its ability to lengthen telomeres, its activity in different types of tumor has been evaluated as a possible factor involved in tumorigenesis. The aim of this study was to assess the prognostic significance of telomerase activity in patients with colorectal carcinoma. Patients and Methods: Telomerase activity was determined in 103 patients undergoing surgery for colorectal cancer between 2001 and 2003. Telomerase activity was determined by an enzyme-linked immunoassay based on the amplification of telomeric repeat sequences (TRAP assay). Results: 90% of our study population showed telomerase activity. Telomerase activity was related to tumor stage and site: a lower proportion of patients with stage A tumors showed telomerase activity compared to more advanced stages; and more patients with colon than with rectal carcinomas were telomerase positive. Multivariate analysis revealed that by adjusting for tumor stage, telomerase activity could be used to predict the risk of death or recurrence (p < 0.001). Conclusions: Activation of telomerase seems to be a frequent event related to the stage of the tumor in colorectal tumorigenesis. Our findings suggest that telomerase activity can predict a greater risk of death or recurrence, irrespective of the more conventional prognostic factors.