The cystic fibrosis patients can be colonized by Aspergillus, in absence of symptoms, and the usefulness of an antifungal therapy is debated. The diagnosis of Aspergillus disease is difficult for the aspecific respiratory symptoms and for the low sensitivity of the diagnostic tests. The objective of the study is to increase the sensibility of Aspergillus infection diagnosis using the combination of different diagnostic tests and to identify patients that could improve with an antifungal therapy. The study will enroll 18 years-old CF patients, referring to four Italian Cystic Fibrosis Center. The enrolled patients (nearly 400) will perform a sputum sample for microbiological culture, galactomannan detection and Aspergillus real-time PCR, and a blood test for detection of specific IgE and IgG. The patients will be classified according to the results of the tests, evaluated for the prescription of antifungal therapy, treated when necessary and prospectively monitored. The study may be useful for understanding the role of Aspergillus in the evolution of CF lung disease and may guide the decision of clinicians to prescribe antifungal therapy.