A total of 153 diagnostic bone marrow biopsies from patients with advanced stages of multiple myeloma corresponding to stages II and III according to the Durie/Salmon classification were evaluated prior to any treatment in a prospective therapy trial of the German Myeloma Treatment Group. Histologic sections were analyzed according to a pre-defined system of criteria microscopically by 2 observers, determining three criteria: 1) grading by histopathology, regarding the cytologic differentiation of neoplastic cells and quantifying the percentage of plasmacytic, pleomorphic, and plasmablastic myeloma cells distributed within the sections; 2) the volume of infiltration; and 3) the pattern of neoplastic growth. Furthermore, four other criteria, namely hematopoiesis, fiber increase, osteomalacia, and micro-osteo-lesions, were evaluated. A cluster analysis using the three histological criteria revealed three groups of patients with significantly different survival times based on histological criteria only; the three criteria were mentioned above. It is concluded from these results that bone marrow biopsies, when evaluated histologically by grading and staging according to the three criteria, provide most valuable prognostic parameters in myeloma patients.