The diagnostic criteria of the Polycythemia Vera Study Group (PVSG) do not include bone marrow (BM) examinations. The aim of this review is to elucidate whether distinctive patterns of histopathology exist which discriminate reactive (secondary polycythemia) from autonomous (polycythemia vera) erythrocytosis. When accompanied by an elevated platelet count, the initial stages of PV may clinically mimic essential thrombocythemia because they are not recognized by the conventional diagnostic criteria. Our data are derived from previous studies and evaluations of 362 patients with a borderline to marked increase in hemoglobin. PV revealed a trilineage myeloproliferation (panmyelosis) with a pleomorphous appearance (ie, differences in size) of loosely clustered megakaryocytes that failed to show gross cytological anomalies. Distinction from SP was accomplished by regarding megakaryopoiesis and the stromal changes (perivascular plasmacytosis, eosinophils, cell debris, and iron deposits). Discriminant analysis of standardized BM features, based on semiquantitative evaluation, yielded a sensitivity of 96% concerning the clear-cut separation of PV from SP.