The aim of the study was to analyze differences in the serum levels of 8 selected biological parameters between monoclonal gammopathy of undetermined significance (MGUS) and different stages of multiple myeloma (MM), potentially beneficial for distinguishing between the two conditions. The analyzed group of 131 subjects comprised 62 individuals with MGUS and 69 MM patients examined at the time of diagnosis. The serum levels were determined by a quantitative immunoradiometric assay (insulin-like growth factor 1, IGF-1) and quantitative sandwich enzyme immunoassay (osteopontin, OPN; endostatin, ES; macrophage inflammatory proteins 1α/β, MIP-1α/β; angiogenin, ANG; and interleukin 17, IL-17). The analysis showed a statistically significant difference in serum concentrations between MGUS and the symptomatic form of MM using the Durie-Salmon (D-S) staging system only in the cases of OPN and stages II and III (0.001 and MM. More benefit may be expected from analyses using multiparametric immunophenotyping of plasma cells and molecular biology methods including gene expression analysis and proteomics.