A Japanese man in his 60s on medication for chronic lymphocytic leukemia presented with progressive, multifocal neurological manifestations. Magnetic resonance imaging showed a small, solitary region of brainstem involvement. Sensitive real-time polymerase chain reaction testing detected a small amount of JC virus (JCV) DNA (170 copies/mL) with pathogenic mutation in cerebrospinal fluid. We diagnosed the patient with progressive multifocal leukoencephalopathy (PML). The small PML lesion may have caused multifocal neurological symptoms because of its focal brainstem involvement. This case contributes to knowledge regarding the diagnosis and treatment of brainstem PML in the context of hematologic malignancies and other underlying diseases.