Granulomatous lung diseases include a large number of conditions among granulomas are the pathological hallmark. Some of these conditions are frequently encountered in clinical practice. Differentiating infectious from noninfectious forms is a priority for the different specialists approaching these diseases, given the different implications for management and treatment. However, differential diagnosis is not always straightforward and the diagnosis of granulomatous disease, considering separately the clinical, radiological and pathological aspects, is at times incomplete or uncertain and requires multidisciplinary assessment. In this paper, we propose a combined HRCT-pathological approach to assess both the topographical and morphological features of the lesions. Based on topography, we can distinguish between granulomatous lesions distributed along the lymphatic vessels, with random distribution or centred on the airways. The prototype of the disease with lymphatic granulomas is sarcoidosis. In contrast, diseases exhibiting a random distribution of granulomas are those with haematogenous spread, the most typical of which is miliary tuberculosis (TB). Many diseases have distribution along the airways including hypersensitivity pneumonia and granulomatous bronchiolitis (including infections with bronchial spread, especially mycobacteriosis). The anatomical approach is completed by the assessment of the morphological aspects of the lesions and associated signs, reflecting both the possible mechanisms of spread and the different types of pathological and/or reparative tissue related to the disease.