Smouldering multiple myeloma (SMM) presents without MM defining symptoms. We aimed to identify patients with SMM with an 80% risk of progression within 2 years using only serum parameters. In total, 527 patients with SMM were included and divided into a training group (287 patients from the Czech Myeloma Group [CMG]) and an independent validation group (240 patients from Heidelberg). The median follow-up was 2 center dot 4 and 2 center dot 5 years, respectively. Progression to MM occurred in 51 center dot 9% of the CMG and 38 center dot 8% of the Heidelberg patients, respectively. The median risk of progression was 11 center dot 0% (CMG) and 9 center dot 7% (Heidelberg) per year, during the 5 years after diagnosis. A serum involved/uninvolved free light-chain ratio of >30, immunoparesis, and serum monoclonal (M) protein of >= 2 center dot 3 g/dl emerged as powerful predictors of 2-year progression rate with a hazard ratio (HR) of 2 center dot 49 (95% confidence interval [CI] 1 center dot 49-4 center dot 17), HR of 2 center dot 01 (95% CI 1 center dot 36-2 center dot 96) and HR of 2 center dot 00 (95% CI 1 center dot 44-2 center dot 79) (P < 0 center dot 001) in univariate Cox regression analysis, respectively. Based on this, the CMG model identified patients with SMM with a 2-year risk of progression of 78 center dot 7% (95% CI 53 center dot 1-95 center dot 7; HR 6 center dot 8;P < 0 center dot 001, CMG) and 81 center dot 3% (95% CI 47 center dot 1-98 center dot 8; HR 38 center dot 63;P < 0 center dot 001, Heidelberg). Serum parameters in the CMG model allow identification of patients with SMM with an 80% risk of progression to symptomatic MM within 2 years.