Diffuse cystic lung diseases (DCLDs) represent a heterogeneous nosological group with a common radiological characteristic in the form of multiple lumens filled with air and surrounded by walls with adjacent intact pulmonary tissue. Most patients with DCLDs have one of four diseases — lymphangioleiomyomatosis, Langerhans cell histiocytosis, Bert-Hogg-Dubé syndrome and lymphocytic interstitial pneumonia, however sometimes differential diagnosis may require the exclusion of other rare diseases. High-resolution computed tomography (HRCT) has importance in DCLDs assessment, and cysts’ characteristics such as shape, size, distribution and other associated radiological features, can help in the differential diagnosis of DCLDs, that remains one of the most challenging clinical tasks. Diagnosis of DCLDs should begin with an integral analysis of clinical, anamnestic and X-ray manifestations of the disease, characterized by various HRCT features and directed search for extrapulmonary signs, including skin, pleural and intra-abdominal manifestations, which allow to limit the differential-diagnostic range of possible DCLDs.