Aim of this work was to assess the predictive value of micronuclei (MN) frequency in peripheral blood lymphocytes (PBL) for the risk of cancer death in disease-free individuals. Blood samples from 1650 subjects selected from the general population of Pisa, Italy, were collected between June 1991 and November 1993. The follow-up until January 2005 recorded a total of 111 deaths (52 for cancer). MN frequency was assessed for 49 cancer cases and 101 matched controls. A significantly higher MN frequency was found in cancer cases (4.7+/-3.4 MN/1000 BN cells) versus controls (1.5+/-1.7; p<0.0001). Donors were stratified in two classes and multivariate logistic regression analysis confirmed that individuals with high MN frequency (>2.5 MN/1000 BN cells) had a significantly increased risk of cancer death (OR=10.7; 95% CI=4.6-24.9; p<0.0001) when compared to individuals with low MN frequency (<or=2.5 MN/1000 BN cells). Ageing was associated with a 6% increased risk per year (p=0.03). No influence of other potential confounders (gender, occupation, smoking and drinking habits) was observed. Finally, subjects with a higher MN frequency showed a higher MR for CVD (Logrank test, p=0.001). These findings provide strong evidence that MN frequency assessed in PBL of disease-free subjects is a good predictor of cancer death risk, evaluated by a nested case-control study performed 14 years after the original recruitment.