Background: IL-6, IL1-beta, TNF-alpha and IL-21 have been identified in the growth, progression and dissemination of multiple myeloma. To dte, there is no published data about serum levels of IL-21 in patients with multiple myeloma. In the present study we have investigated circulating levels of cytokines, such as IL-6, IL-1 beta, TNF-alpha, IL-21 and the association of these levels with the disease stage in newly diagnosed multiple myeloma patients. Materials and Methods: Twenty healthy controls and 44 newly diagnosed multiple myeloma patients were evaluated. Patients were classified according to Durie-Salmon criteria, international staging system (ISS) and bone disease. Quantification of cytokine levels in serum were performed by using ELISA. Results: The levels of cytokines in patients' serum are found elevated than healthy controls. However, only the serum levels of IL-1 beta and TNF-alpha were found statistically significant. TNF-alpha levels of patients with ISS stage 3 were significantly higher than patients with ISS stage 1 and 2 (P 0.000). IL-1 beta was significantly elevated in advanced stage patients (stage II-III) (P 0.040). There was no correlation between IL-1 beta, TNF-alpha, IL-21 levels and bone lesions. IL-6 levels were significantly elevated who have at least three visible lytic bone lesions and/or bone fracture in comparison to patients who have one or two visible or no visible lytic bone lesions (P 0.048). Conclusion: It appears that there is no association of serum IL-21 level with multiple myeloma in contrast to the other cytokines such as IL-6, IL-1 beta, TNF-alpha.