Although multiple sclerosis (MS) is an immune-mediated disorder, serological testing to aid in its diagnosis has not been developed. To test the hypothesis that the pathological changes in MS can be detected by analyzing a molecular signature of serum proteomic patterns, we tested sera from 25 newly diagnosed relapsing-remitting MS patients and 25 healthy controls with matrix-assisted laser desorption/ ionization time of flight (MALDI-TOF) mass spectrometry, following albumin depletion and desalting. Analysis of MALDI-TOF/mass spectrometry data, using proteomic spectral pattern recognition software, revealed a distinct proteomic pattern in the MS group determined by 3 biomarkers at 8687, 8773, and 8818 mass-to-charge ratios. Although our data are representative of analysis on a small number of samples and are preliminary, we conclude that MALDI-TOF/mass spectrometry, in combination with serum proteomic pattern analysis, could be useful in the diagnosis of MS, and a larger, masked trial to identify proteomic spectral patterns characteristic of relapsing-remitting, primary progressive and secondary progressive variants of MS is justified.