A 21-year-old woman with a 6-year history of SLE presented with a speech disturbance and right hand clumsiness along with manifestations of active disease suggesting central nervous system SLE. Despite aggressive treatment for SLE, her neurological condition worsened. MRI demonstrated low intensity in T1-weighted images and high intensity in T2-weighted images in the white matter of the bilateral cerebrum and cerebellum, compatible with progressive multifocal leukoencephalopathy (PML). Intraspinal administration of interferon-beta seemed to slow the deterioration of her MRI and neurological findings. However, she eventually developed decerebrate rigidity and died due to candidemia. DNA of the JC virus was detected in the autopsied brain by the polymerase chain reaction technique. PML should always be borne in mind when examining patients with SLE showing neurological abnormalities.