Fatigue in multiple sclerosis (MS) may be attributed to a variety of biological and psychological factors. Scales addressing the multidimensionality of fatigue are used in MS evaluation, although adequacy of data on their reliability and validity is questionable. The aim of the present study was to provide evidence for the validity and reliability of the Greek version of the Modified Fatigue Impact Scale (MFIS). The MFIS was translated into Greek and administered to 99 MS patients and 75 controls. Exploratory factor analysis was carried out and reliability measures were calculated. Discriminant validity was also assessed. The mean MFIS score was 33.8 (SD 17.8). Two factors (physical and cognitive) were extracted through factor analysis; a psychosocial factor was not identified. Reliability measures (intraclass correlation coefficient, Cronbach's α, Pearson's correlation) yielded high values. Patients and nonpatients differed statistically significantly in the MFIS scores; no statistically significant differences in MFIS score according to the type of MS were observed. It can be concluded that the Greek version of MFIS is valid and reliable, although questions about the scale dimensions remain. Further modifications and cultural adaptation of the scale may help create a useful tool for screening and assessment of fatigue in MS patients.