BACKGROUND: The aim of this study was to determine the prevalence of altered immunological tests and their clinical significance in patients with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS). ----- PATIENTS AND METHODS: The information was gathered from medical records of patients hospitalized in the Referral Center for Demyelinating Diseases in the 2008-2010 period. All patients had ANA, ENA profile, ANCA, aCl IgG and IgM, C3, C4, CH50, anti-TPO, AST and RF antibodies tested. ----- RESULTS: From 726 patients with CIS that were reviewed, the complete battery of immunological tests was performed in 418 of them (57.6%), representing our cohort. Altered tests were found in 235 patients (56.2%); 73 (17.4%) had positive antinuclear antibodies, 14 (3.3%) had positive ENA, 47 (11.2%) had positive aCl IgG, 83 (19.8%) had positive aCl IgM, and 13 (3.1%) had anti TPO antibodies. We found no correlation between ANA, aCl IgG or IgM positivity (ANA vs aCL IgG p=0.554; ANA vs aCL IgM p=0.19; aCL IgG vs aCL IgM, p=0.155). None of the patients had any clinical manifestations other than MS symptoms. ----- CONCLUSION: These results indicate that significant number of patients with CIS have altered immunological tests but nevertheless none of them had clinical expression of any other autoimmune disease making them clinically insignificant. In conclusion there is no need to perform extensive immunological work-up in all patients with CIS. Contrary, our results argue for more focused testing rather than a battery of screening tests.