Recently, the number of previously asbestos-exposed workers performing, at our department, medical exams aimed at an early diagnosis of asbestos-related tumors, has been progressively increasing. The diagnostical protocol we propose to these subjects include both radiological exams and some serum markers such as mesothelin and osteopontin. In this case-report we illustrate the history of a worker who, after having diagnosed a pulmonary asbestosis, developed a Lung Cancer. The significance of this case is based on the importance of the high mesothelin dosage which prompted further radiological exams resulting into the final diagnosis. In spite of the early diagnosis and treatment the patient finally died. Nevertheless, serum markers like mesothelin and osteopontin (especially the first) may result very helpful in monitoring and screening the population of workers previously exposed to asbestos.