To determine some of the key clinical features that help prompt clinicians to pursue additional work-up for evaluation of CNS involvement of MF, we conducted a systematic review to better define characteristics, treatments, outcomes, and mortality in these patients. Our analyses indicated that neurologic surveillance after the diagnosis of MF is crucial. Review of systems should include change in mentation, vestibular, and ocular symptoms. Progression to CNS involvement does not always occur in tandem with cutaneous disease burden. Single-agent therapies can delay disease progression and improve prognosis. Multi-agent treatment does not improve survival.