Clinical staging systems for multiple myeloma published so far have not always been reliable in predicting a prognosis and do not provide important insights into the biology of the disease. Therefore, new single independent factors or their combination are needed in order to define prognostic subgroups. This is especially necessary with respect to the two treatment options such as a 'watch and wait' strategy vs autologous or even allogeneic bone marrow or stem cell transplantation. At the moment the most promising parameters for future trials and treatment decisions seem to be the plasma cell labeling index, the beta2-microglobulin and hopefully cytogenetic abnormalities that are detectable in multiple myeloma now using newer cultivation methods and fluorescence in situ hybridization in interphase plasma cells. Therefore, it is necessary to focus on these latter prognostic parameters in prospective trials when newer approaches with potentially curative therapies are administered.