Fotemustine is a cytotoxic drug belonging to the group of nitrosourea derivatives, and is used in the treatment of metastatic melanoma, particularly when secondary brain lesions are present. We report the case of a female patient in partial response following 10 courses of fotemustine and featuring a rapidly progressing mental impairment. The clinical and radiological patterns were consistent with a fotemustine-related toxic encephalopathy, as described previously in a recent report. The physician should be aware of this neurological complication of fotemustine, so that it may be recognized early and not attributed erroneously to tumour evolution.