Introduction: The presence of oligoclonal bands in cerebrospinal fluid of multiple sclerosis patients is now well established to support the clinical diagnosis. On the other hand, a single band response can represent the initial stage of an oligoclonal response, before the other antibody clones become visible. Method: The aim of the current study was to evaluate the presence of an isolated cerebrospinal fluid single immunoglobulin band, and to analyse the clinical and radiological diagnosis of the samples with a single immunoglobulin band. In this study, 3524 cerebrospinal fluid samples were re-examined using agarose gel isoelectric focusing, and ones with an isolated cerebrospinal fluid immunoglobulin band were detected. Results: A single band in cerebrospinal fluid was detected in 1.4% samples. A clinically isolated syndrome was diagnosed in 27.5%of them, relapsing remitting multiple sclerosis in 49%, secondary progressive multiple sclerosis in 11.8%, and radiologically isolated syndrome in 2%. No primary progressive multiple sclerosis patient was found. All Barkhoff criteria were met in 90.1% of them. The remaining were diagnosed with other inflammatory neurological diseases (9.8%). Conclusion: The presence of an isolated cerebrospinal fluid monoclonal immunoglobulin band is rare. Although most of the samples were diagnosed as multiple sclerosis according to both clinical and paraclinical (magnetic resonance imaging) parameters, they had only a single immunoglobulin band in cerebrospinal fluid. Not only oligoclonal bands, but also an isolated cerebrospinal fluid single band might be a cornerstone for the diagnosis of multiple sclerosis at least for some patients.