To investigate the role of telomerase in the multistep colorectal carcinogenesis, we examined telomerase activity in 31 adenomatous polyps and 22 paired cancer-normal mucosa specimens from non-hereditary nonpolyposis colorectal cancer patients. Telomerase activity was detected in 18% of normal mucosa, 16% of small (<1.0 cm) polyps, 20% of intermediate polyps, 71% of large (>2.0 cm) polyps, and 96% of adenocarcinoma samples (P for trend, <0.0001). High-level enzyme activities were seen in none of the normal mucosa, 5% of small polyps, 20% of intermediate polyps, 43% of large polyps, and 73% of adenocarcinoma samples (P for trend, <0.0001). These data indicate telomerase reactivation occurs with adenomatous polyp progression in multistep colorectal carcinogenesis.