Using age, hemoglobin level, platelet count, serum β2-microglobulin and monoclonal protein concentrations, the International Scoring System for WM (ISSWM) has been specifically designed for predicting survival after the initiation of first-line therapy. Five-year survival rates of low-, intermediate-, and high-risk patients were 87%, 68%, and 36%, respectively. The aim of the present review was to assess the applicability of this statistical model for making treatment decision in clinical practice, despite the difficulties posed by the characteristics of this rare disease. Finally, we propose that the distribution of ISSWM subgroups should be reported in any treatment reports.