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Isolated CNS relapse post ASCT is extremely rare in multiple myeloma and portends a poor prognosis. A 29-year-old-male was diagnosed with multiple myeloma, IgG Kappa, ISS-III, extramedullary disease (paraparesis) with renal dysfunction. He was treated with induction chemotherapy (VCD) with which he attained hematological CR with incomplete neurological and renal recovery. He underwent ASCT with melphalan. He had CNS only relapse within six months post-transplant with multiple intraparenchymal and extradural lesions. He did not respond to whole brain radiation, intrathecal methotrexate and thalidomide based (given on basis of anecdotal evidence of efficacy of immunomodulators) and succumbed to his disease.