A 68-year-old man was presented with high fever of unknown origin for 3 weeks and non-productive cough for 1 week. A chest computed tomography (CT) scan revealed multiple nodules and ground glass opacities (GGO) in both lungs. The patient was initially diagnosed with hypersensitivity pneumonitis based on the result of bronchoalveolar lavage fluids (BALF). After treatment with methylprednisolone for 2 weeks, the patient's fever recurred, with no resolution of lesions on chest CT. The patient consented to positron emission tomography (PET)/CT. It showed that fluorodeoxyglucose (FDG) metabolism was significantly increased in the spleen, whole skeleton, and both lungs, suggesting a malignant hematological disease. Large B-cell lymphoma was diagnosed by bone marrow puncture and flow cytometry. Transbronchial lung cryobiopsy was performed to evaluate the diffuse lung lesion. Hematoxylin-eosin (HE) staining showed diffuse infiltration of heterotypic cells in the pulmonary interstitial capillaries. Furthermore, immunohistochemical examination results suggested lung infiltration of B lymphohematopoietic system tumors. The patient was finally diagnosed as intravascular large B-cell lymphoma (IVLBCL). IVLBCL with diffuse lung ground glass lesions is very rare and difficult to diagnose. Transbronchial lung cryobiopsy, as an emerging procedure, plays an important role in the diagnosis of interstitial lung disease and has gained popularity for a lower complication rate and acquisition of more tissue samples.