There are no well-defined host markers to determine which patients with a diagnosis of monoclonal gammopathy of undetermined significance (MGUS) will progress to multiple myeloma (MM). In this preliminary study we measured plasmatic soluble Fcγ receptor type III (sFcγRIII or sCD16) in 54 individuals with MGUS, 35 patients with multiple myeloma (MM) and 29 healthy controls. We confirmed, through receiver operating characteristic (ROC) curve analysis, that a low level of sCD16 discriminates MM patients from controls. Indeed, for a sCD16 value of 1.3 μg/ml, the sensitivity, as well as the specificity, of this discrimination were both equal to 83%, i.e. 83% of MM patients had a plasmatic sCD16 value <1.3 μg/ml compared with only 17% of controls. Moreover, ROC curve analysis showed that a low sCD16 level also identifies among MGUS patients a subgroup of patients who rapidly progress towards multiple myeloma: in this comparison, for a sCD16 level of 1.3 μg/ml, sensitivity and specificity were 70% and 79% respectively. Therefore a low sCD16 level in MGUS indicated a high likelihood of rapid evolution to MM. In contrast to sCD16, soluble IL-6R did not appear to be discriminant in this study.