B cell-activating factor (BAFF) is a cytokine that plays a major role in the maintenance of normal B-cell development and homeostasis. It has been suggested that in multiple myeloma (MM) it might have regulatory effects on the proliferation and viability of malignant plasma cells. The aim of this study was to evaluate serum levels of BAFF in 52 newly diagnosed MM patients, with varying disease severity, in order to see the correlations between BAFF and indices of MM activity, such as interleukin-6, C-reactive protein, lactate dehydrogenase, and beta-2 microglobulin, and to explore the clinical significance of BAFF in predicting the disease activity of MM. We found increased BAFF serum levels in MM patients, increased in advanced stages, and decreased in plateau phase. We also found significant correlations between BAFF serum levels with the above parameters of disease activity. We conclude that BAFF may play an important role in pathogenesis of MM, could be used as a marker of disease activity, and a possible therapeutic target.