A 71 year-old woman had intermittent pyrexia (>38 C) for 1 week in May 2009. Her family doctor treated her with a course of antibiotics to no effect. Computed tomography (CT), cardiac ultrasonography, and tuberculosis skin test detected no abnormalities. General malaise gradually developed, and hemoglobin (Hb) level fell from 10.2 g/dL to 9.0 g/dL over 2 weeks. She was admitted to our hospital as a case of fever of unknown origin. On admission, pyrexia was the only abnormality on vital signs. She was taking no medications other than verapamil and digoxin for paroxysmal supraventricular tachycardia. Meticulous physical examination detected anemic conjunctivae and edema of the bilateral lower extremities. No skin lesions, palpable lymph nodes, or neurological abnormalities were evident. Laboratory findings showed anemia (Hb, 8.8 g/dL) and elevated levels of lactate dehydrogenase (454 IU/L) and soluble interleukin-2 receptor (sIL2-R, 6,030 U/mL). Commonly used autoantibodies and tumor markers for assessment of collagen diseases and cancers were all negative. CT scan revealed no lymphadenopathy, hepatosplenomegaly, or abnormal lung lesions. Gallium scintigraphy showed no abnormal accumulations. Brain magnetic resonance imaging (MRI) revealed a non-enhancing, high-intensity area of 17 mm in diameter in the pons on T2- and diffusion-weighted imaging (Figure 1A and B); however, no abnormal neurological signs were observed. Cerebrospinal fluid examination likewise found no abnormalities. Based on the high sIL2-R level, IVLBCL was suspected. A bone marrow biopsy showed a normocellular marrow with no apparent lymphoma cells. Genetic analysis of the bone marrow specimen showed no clonal rearrangement of T-cell receptor Cbeta1 or the immunoglobulin heavy chain JH region gene. We took healthy-appearing skin randomly from the forearm, lower abdomen, and thigh for biopsy although no skin lesions were observed. All specimens revealed large B lymphoma cells within small veins and capillaries of the subcutaneous fat tissues but not outside the vessels (Figure 2A and B). Immunohistochemical studies showed that lymphoma cells were positive for CD20 (Figure 3), a B-cell marker, and negative for CD3, a T-cell marker. Based on these findings, a diagnosis of IVLBCL was made. The patient's poor general condition required a less toxic regimen, thus conventional R-CHOP therapy, consisting of rituximab (375 mg/m2), cyclophosphamide (750 mg/m2), doxorubicin (50 mg/m2), vincristine (1.4 mg/m2), and prednisolone (60 mg/m2), was started within 1 month of initial symptoms. After the first lumbar puncture for spinal fluid examination, the patient did not accept repeating it due to its invasiveness. For this reason, we treated the patient without any intrathecal treatment. After the first cycle of systemic chemotherapy, the patient had resolution of fever and peripheral edema, as well as improvement in Hb, lactate dehydrogenase, and sIL2-R levels. After eight cycles of R-CHOP therapy, the pontine lesion had completely disappeared (Figure 4A and B). Therefore, the asymptomatic reversible pontine lesion was considered as IVLBCL involvement. During follow-up, the value of sIL2-R had been within reference range. Currently at 5 years after diagnosis, the patient has been doing well with no recurrence and returned to work without any neurological disorders.