A 73-year-old man presented with dyspnea and hypoxemia. The patient was admitted to our hospital because he had been experiencing dyspnea for the past 2 weeks at rest as well as during exertion. He had no history of smoking. On physical examination, the patient had a body temperature of 36.7 °C, blood pressure of 151/89 mmHg, heart rate of 122 beats/min, respiratory rate of 21 breaths/min, and oxygen saturation of the peripheral artery of 88% (room air). On auscultation, no heart murmur was heard and lung sounds were clear. Laboratory findings showed an increased lactate dehydrogenase (LDH) level of 1690 U/L (normal: 130–235 U/L) and soluble interleukin-2 receptor (sIL-2R) level of 1140 U/mL (normal: 157–474U/mL). We initially suspected pulmonary artery thromboembolism. Therefore, we performed a dual-energy Computed tomography (CT) scan, including the pulmonary artery phase. CT showed patchy ground-glass opacities predominantly in both upper lobes of the bilateral lungs. The pulmonary artery phase of CT showed no dilatation of the main pulmonary artery trunk diameter and no contrast defects within the pulmonary arteries. Dual-energy CT iodine mapping showed a significant symmetrical decrease in iodine distribution in the upper lungs, suggesting an unusual distribution of pulmonary hypoperfusion. We suspected intravascular large B-cell lymphoma (IVLBCL) based on the patient’s history of dyspnea for the past 2 weeks with no history of cancer, decreased peripheral perfusion of the lung parenchyma on CT, and elevated LDH and sIL-2R levels on laboratory findings. Three days after admission, a random skin biopsy was performed. Atypical cells were present from the dermis to subcutaneous vessels, leading to the suspicion of lymphoma. Immunostaining showed that the atypical cells were CD5 +, CD20 +, CD79a +, CD3-, and CD30-; therefore, the diagnosis of IVLBCL was confirmed. Due to the severity of the disease, lung biopsy was averted. After admission to the hospital, high-dose methotrexate was administered for central nervous system involvement based on the findings of suspected intracranial infiltration on a brain magnetic resonance imaging and elevated cell counts on lumbar puncture. Subsequently, oxygen demand improved, and rituximab along with cyclophosphamide, doxorubicin, vincristine, and prednisone was added to the patient’s regime. Eventually, oxygen administration was terminated, the patient’s general condition improved, and the patient was discharged after 47 days of hospitalization.