Telomeres are the end regions of linear chromosomes, and in normal somatic cells the lengths of telomeres shorten with successive cell divisions. Telomerase, a ribonucleoprotein enzyme, maintains the length of telomeres in immortal and germline cells. Although present in human fetal tissues, shortly after birth telomerase activity is not detectable except in germline cells, hematopoietic cells, and most human primary tumors. In the present study we show telomerase activity to be present in 73 of 77 basal cell carcinomas, 15 of 18 nonmetastatic cutaneous squamous cell carcinomas, and 6 of 7 cutaneous melanomas, contrasting with extremely low levels detected in sun-protected skin. Sun-damaged skin, psoriatic lesional skin, and skin from lesions of poison ivy dermatitis, however, have increased levels of telomerase activity compared to sun-protected skin, although less than that detected in tumor tissue. Because telomerase activity can be found in inflammatory lesions of the skin, this indicates that telomerase activity does not always correlate with the malignant phenotype. In addition, we show that telomerase activity is localized to the epidermis of newborn foreskin, which suggests that telomerase is expressed constitutively by cells in the epidermis. Finding higher levels of telomerase activity in sun-exposed skin compared to nonexposed skin suggests that environmental factors may modulate telomerase activity.