Telomerase is an enzyme that causes short repeated sequence addition to the ends of chromosomes, thereby preventing their shortening during cell division and counteracting cell senescence. Telomerase activity is generally absent in adult differentiated cells, whereas it has been demonstrated in tumor cells, suggesting that its presence might be considered an index of malignancy. To evaluate whether telomerase might be considered a good predictive index of malignancy in adrenocortical tumors, we measured telomerase activity in 11 adrenal adenomas and 7 carcinomas obtained at surgery, using an original quantitative method. Telomerase activity was significantly higher (P<0.001) in carcinomas than in adenomas (median, 15.2 ng DNA/microg protein; range, 9.0-27.6 vs. 2.0; range, 0-8.3), and no overlap was observed between the 2 groups. In carcinomas, telomerase activity was significantly correlated with tumor diameter (r = 0.939; P<0.0001), whereas in adenomas it was not. The results of this study suggest that quantitative telomerase measurement may represent a useful tool to differentiate malignant from benign adrenocortical tumors.