The term “infiltrative lung disease” is used to describe a large spectrum of disorders. They are characterized by a great similarity in their radiologic, physiologic, and clinical presentation. To achieve an accurate diagnosis, performance of histopathologic studies is needed in most of the cases. Lung specimens can be obtained through transbronchial biopsies, but in some instances, open lung biopsies are required. In selected cases, other diagnostic techniques (e.g., high-resolution CT) may help in defining the condition. Many peripheral blood abnormalities may be associated with interstitial lung diseases and may be helpful in screening high-risk individuals searching for disease, in diagnosing disease activity, in monitoring the effectiveness of therapy, or in disclosing the presence of recurrences and/or complications. These serum or blood cell abnormalities should be used together with clinical and imaging data, because their use separately from clinical observations may lead to confusion (e.g., serum angiotensin-converting enzyme in sarcoidosis, serum precipitating antibodies in hypersensitivity pneumonitis, or cytoplasmatic antineutrophil cytoplasmic antibodies (c-ANCA) in Wegener granulomatosis). The sensitivity and specificity may vary widely in accordance with the blood components and the disease under consideration.