The etiological diagnosis of diffuse interstitial lung disease (ILD) is based on the integration of simple information gathered by interview, physical examination and discriminating arguments made by some investigations of the lower respiratory tract (HR-CT scan, pulmonary function tests, biological and bronchoalveolar lavage results). Obtaining the diagnosis of ILD is an important step but lung biopsy is rarely necessary: the key of ILD etiological diagnosis lies to obtain optimal information while imposing minimal patient aggression. The diagnostic approach is best when the case is subject to a multidisciplinary discussion between clinician, radiologist and pathologist experienced in the field of ILD.