Paraneoplastic syndromes (PNS) involving the central nervous system are a rare manifestation of malignant disease. As they commonly precede the diagnosis of malignancy their acute manifestations do not often present themselves to oncologists in the first instance. It is currently believed that most, if not all, neurological PNS are autoimmune in nature. Proteins expressed ectopically on the surface of tumour cells generate an immune response which cross-reacts with the same, or similar, proteins in the nervous system resulting in damage. This can involve a single cell type of the nervous system whilst in other cases the impairment is more widespread. The following report is of a case of chronic inflammatory demyelinating polyneuropathy (CIDP) occurring in metastatic malignant melanoma, following treatment with interferon-alpha. We review the current literature on this rare association and speculate on its pathogenesis, and the implications for future therapeutic strategies in melanoma targeting tumour antigens.