Progressive multifocal leukoencephalopathy is a central nervous system disease due to reactivation of the human polyoma JC virus in immunocompromised patients. Advanced mycosis fungoides patients are intrinsically immunosuppressed and susceptible to infections, but only rarely have been reported to develop progressive multifocal leukoencephalopathy. We report a case of progressive multifocal leukoencephalopathy developing in an advanced mycosis fungoides patient without prior history of immunosuppressive therapy.