Multiple sclerosis is an autoimmune disease of the central nervous system associated with abnormal activation of both cellular and humoral immune responses. B lymphocytes play a key role by crossing the damaged blood–brain barrier and releasing antibodies that contribute to inflammation within the central nervous system. The presence of oligoclonal bands in the cerebrospinal fluid is evidence of intrathecal immunoglobulin synthesis and serves as a recognised biochemical marker of multiple sclerosis. Despite their high sensitivity and specificity, oligoclonal bands have certain limitations. As a qualitative test, they do not reflect the severity of inflammation, are time-consuming and costly, and their interpretation may be subjective and dependent on the experience of the diagnostician. The 2024 revision of the McDonald criteria allows the use of the kappa free light chain index as an equivalent or alternative to oligoclonal band detection. Free kappa light chains, produced in excess by plasma cells, are components of immunoglobulins. Their measurement offers a simpler, faster, and more affordable quantitative method with diagnostic value similar to oligoclonal bands. When present at appropriate levels, they fulfil the criterion of dissemination in time and enable the diagnosis of multiple sclerosis, including in patients with radiologically isolated syndrome, clinically isolated syndrome, and primary progressive multiple sclerosis. Additionally, they may provide prognostic insight. It is suggested that their concentration may help estimate the time to radiological progression, disease relapse, or worsening of disability. Kappa free light chains, especially the calculated index reflecting intrathecal immunoglobulin synthesis within the central nervous system, represent a new and promising diagnostic option in multiple sclerosis, particularly in therapies targeting B lymphocytes.