The reference values (RVs) for blood Cd and Pb of 215 adult subjects non-occupationally exposed and living in Sardinia (insular Italy) were assessed. Age, sex, smoking, alcohol drinking and living area were used to stratify the reference group. After collection from volunteers, samples were acid digested in a microwave oven and metals were determined by sector field inductively coupled plasma mass spectrometry. The RVs expressed as 5th–95th percentiles (geometric mean, GM) were 0.24–1.82 μg/l (0.53 μg/l) for blood Cd and 13.2–87.3 μg/l (33.4 μg/l) for blood Pb. Females had GM levels of Cd (0.58 μg/l) higher than males (0.49 μg/l); subjects aged <40 years had less Cd (0.44 μg/l) than old subjects (>60 years; 0.56 μg/l); Cd in smokers (1.23 μg/l) was 3-times higher than in non-smokers (0.42 μg/l) and correlated with the number of cigarettes per day. The alcohol intake and place of living did not influence blood Cd. The GM values of blood Pb in males (44.4 μg/l) were higher than in females (24.7 μg/l); subjects less than 40 years-old (27.5 μg/l) showed lower Pb than elderly individuals (>60 years, 41.2 μg/l); drinkers (42.2 μg/l) had Pb 2-times higher than non-drinkers (24.4 μg/l). Blood Pb was not significantly affected by smoking and place of living. As revealed by multiple linear regression, the predictor variables were, in order of weight, smoke >> age for blood Cd levels, and sex = age >> alcohol for blood Pb levels.