Spatial-temporal dissemination of neurological signs is an essential criterion for establishing a definite diagnosis of Multiple Sclerosis (MS). Unfortunately, we often observe patients who present a history consistent with MS but without objectivity indicating the presence of at least two or more distinct lesions of Central Nervous System (CNS). In recent years, many Authors have emphasized the use of Multimodal Evoked Responses (MER), Cerebrospinal Fluid (CSF) analysis for the research of Oligoclonal Bands (OB), and Magnetic Resonance Imaging (MRI) as highly sensitive techniques for demonstrating the spreading of the lesions. This study, carried out to evaluate whether the combined use of these three methods would increase the diagnostic MS sensitivity, comprises 62 patients classified in Definite (n = 24). Probable (n = 18) and Possible (n = 20) MS according to the clinical criteria of McAlpine. All our cases fulfilled a complete ER evaluation (VER, SER, BAER), a paired CSF and serum Isoelectric focusing (IEF) and a cerebral MRI. Moreover, IgG Index was also estimated. CSF IEF was the most sensitive test in Definite (91.7%) and Possible (80.0%) MS, nearly followed by MRI (87.5% and 45.0% respectively). VER (87.5% and 60.0%) and SER (87.5% and 65.0%). On the contrary, MRI showed the higher sensitivity in Probable MS (94.4%). The course of the disease influenced only SER and VER in all diagnostic group, while the duration correlated positively with BAER and VER. Only VER and BAER, finally, supplied additional information about the not revealed clinically or by MRI CNS disorders. Thus, our data further emphasize the value of combining these laboratory tests for establishing an early and more accurate diagnosis of MS.