Aberrant CD117 expression is associated with a favorable outcome in multiple myeloma. We analyzed 106 patients with symptomatic multiple myeloma (n= 50), smoldering multiple myeloma (n= 38) and monoclonal gammopathy of undetermined significance (n= 18) to elucidate biological features of CD117+ versus CD117− monoclonal gammopathies. CD117+(mono) clonal plasma cells were detected in 30% symptomatic multiple myeloma, 45% smoldering multiple myeloma and 72% monoclonal gammopathy of undetermined significance patients. CD117 expression was associated with higher percentages of normal bone marrow plasma cells, CD117+ myeloid precursors and CD38+ B lymphocytes in all monoclonal gammopathies. Conversely, the number of bone marrow CD34+ myeloid cells and peripheral blood neutrophils was reduced among CD117+ multiple myeloma but not monoclonal gammopathy of undetermined significance patients.