White matter diseases come with a huge number of differential diagnosis. Diagnostic work up in patients with white matter disease is primarily based on neuroradiological findings. Sometimes those findings could mislead a clinician to the wrong diagnosis and hence to unnecessarily diagnostic procedures. Depending on a diagnosis, white matter lesions could be seen unilaterally or bilaterally. In some patients, unilateral white matter lesions are incidental finding and in those cases are usually stable and do not demand an extensive work-up. They could be a consequence of congenital brain infections or some chromosomal abnormalities. We present a case of unilateral white matter lesion in a 54-year-old woman with mild binocular bluured vision. Due to radiological suspicion of John Cunningham virus infection and suspicion of malignant process extended work up was done. It resulted with no detectable cause of white matter lesion. Moreover, lesion showed no change during thirteen-month follow-up period and patient has remained stable.