OBJECTIVE: Telomeres cap chromosomal ends and help to maintain chromosomal integrity. Telomere shortening may result in chromosomal instability and, ultimately, malignant transformation of cells. It has not been systematically studied whether patients with malignancy have shortened telomeres in their normal, nontransformed cells, which might point to a preexisting disposition for chromosomal instability. METHODS: We designed an (age-) matched pair analysis that compared telomere length in nonmalignant peripheral leukocytes from previously untreated patients who recently developed an aggressive non-Hodgkin's lymphoma, with leukocytes from healthy individuals. RESULTS: Telomere lengths in B and T lymphocytes as well as granulocytes from the patients' group were significantly shorter than those from age-matched healthy controls. We were able to rule out increased proliferation, telomerase defects, or increased oxidative stress in patients as confounding factors of shortened telomeres. CONCLUSION: Short telomeres in nontransformed leukocytes may constitute a risk factor for lymphomagenesis.