Cognitive dysfunction involves 40–65 % of multiple sclerosis (MS) patients. It can be detected in all MS phenotypes from the early stages of the disease, and it tends to progress over time. Minimal Assessment of Cognitive Function in MS (MACFIMS) has been proved to be the most sensitive and comprehensive battery available for MS cognitive assessment in the English population. In Italy, MACFIMS applicability is limited in everyday clinical practice since the overall validity of this battery in the Italian MS population has never been demonstrated. The aim of this study was to translate/cross-culturally adapt and validate an Italian version of the MACFIMS. A total of 130 MS patients and 60 healthy controls (HCs) were enrolled and evaluated with an Italian version of the MACFIMS. All tests discriminated MS patients from HCs; according to the literature, approximately more than half of MS patients (70.8 %) exhibit cognitive impairment. Principal component analysis showed four distinct components: visual–spatial memory/processing speed, working memory, executive functions and verbal memory. Our study is the first to validate an Italian version of the MACFIMS. Several aspects of validity have been demonstrated: criterion and, partially, construct. Future work will investigate the longitudinal course of neuropsychological dysfunction in Italian MS patients using these measures.