The activity of telomerase, a ribonucleoprotein maintaining the length of chromosome ends (telomeres) to levels allowing cells to replicate indefinitely, is undetectable in normal, differentiated cells, is present at low levels in some activated cell types (including endothelial cells) and it is highly expressed by tumor cells. Kaposi's sarcoma (KS), the most frequent tumor in Acquired Immune Deficiency Syndrome (AIDS) patients (AIDS-KS), arises as a disorder of new blood vessel formation (angiogenesis), but it may evolve into an aggressive cancer, characterized by the proliferation and invasion of spindle-shaped, endothelial-like cells (KS cells, KSC). Here we report that primary KSC express low telomerase levels which are strongly enhanced by KS initiation and progression factors including the inflammatory mediators interleukin (IL)-1beta, tumor necrosis factor (TNF)alpha and interferon (IFN)gamma, the angiogenic basic fibroblast growth factor (bFGF) and the Tat protein of Human Immunodeficiency Virus (HIV)-1. Noteworthy, the increase of telomerase activity promoted by these molecules parallels the induction of KSC growth and invasion. These preliminary in vitro findings encourage measuring telomerase activity in AIDS-KS lesions in order to survey the clinical progression of the disease.