The present study explored the impact of two novel criteria; having >95% abnormal plasma cells by flow cytometry at diagnosis and the evolving subtype of the disease, as predictors of progression in 61 smouldering multiple myeloma (SMM) and 311 monoclonal gammopathy of unknown significance (MGUS) patients. Although both criteria were of prognostic value, the risk of progression was better identified by immunophenotyping [Hazard Ratio (HR) 6.2 and 17.2 for SMM and MGUS, respectively] than evolving subtype, which had independent prognostic value only in MGUS (HR 3.6). Immunophenotyping discriminated the different risk of progression within the evolving and non-evolving subgroups of SMM (P = 0.01) and MGUS (P < 0.001).