A 60-year-old Japanese man with a history of heavy smoking came to our hospital for a detailed examination, suspecting interstitial pneumonia because of gradually increasing dyspnea on exertion over a period of one year. Chest high-resolution computed tomography revealed ground-glass shadows with emphysematous changes. Pathological analysis of samples obtained using transbronchial lung cryobiopsy revealed an accumulation of alveolar macrophages with abundant eosinophilic cytoplasm in the alveolar space. Following a multidisciplinary discussion, the patient was diagnosed with desquamative interstitial pneumonia. To our knowledge, this is the first detailed report of desquamative interstitial pneumonia diagnosed using transbronchial lung cryobiopsy.