High dosages of Serum Mesothelin have been demonstrated to be significantly associated to Pleural Malignant Mesothelioma. We recently demonstrated that Serum Mesothelin may be clinically helpful both for diagnostic and prognostic purposes, with the best cut-off corresponding to 1 nM. We also discovered that high levels of Serum Mesothelin are significantly associated to Lung Cancer. The usefulness of this marker in secondary prevention has been suggested, though never demonstrated. We therefore started a long-term prospective cohort study including previously asbestos-exposed workers. These subjects periodically underwent both radiological tests and serum mesothelin dosages. As a mid-term goal of this longitudinal study we decided to check the variability of mesothelin dosages, comparing baseline and follow-up values, as well as the possible correlation with age, duration of exposure, smoking, any abnormality of respiratory functional tests (RFT) and/or radiological tests. At baseline, Mesothelin mean value was 0.66 +/- 0.4 (range 0.08-2.2 nM). Both age (p = 0.04) and abnormal thoracic TC (p = 0.04) were significantly correlated with increased serum mesothelin levels and increasing age. No association was found between baseline mesothelin levels and duration of asbestos exposure (p = 0.5), smoking habits (p = 0.2), abnormal RFT, DLCO (carbon monoxide diffusing capacity) or thoracic X-ray. No significant variation was observed between mesothelin values at baseline and at follow-up (p = 0.2).