Abstract: The diagnosis of interstitial lung diseases (also known as diffuse parenchymal lung diseases) which often needs to be established by lung tissue biopsy, is a challenge for respiratory physicians. Different biopsy me-thods including transbronchial lung biopsy(TBLB), percutaneous lung biopsy, and video-assisted thoracoscopic lung biopsy(VATS), all have their specific indications based on patients’ clinical manifestations and radiological features. For diffusely distributed lesions, the minimally invasive TBLB may be considered as the first choice, followed by percutaneous lung biopsy or VATS if the tissue is not adequate to establish the diagnosis. It is noteworthy, for many interstitial lung diseases, a pathological result is not the final diagnosis. The establishment of the diagnosis requires a combination of clinical and radiological findings, the so-called clinical-radiological-pathological (CRP) diagnosis.