The bone marrow criteria defined by the World Health Organization (WHO) are based on characteristic increase and clustering of morphologically abnormal enlarged megakaryocytes as a pathognomonic clue to describe three distinct phenotypic entities of myeloproliferative disorders (MPDs): (1) essential thrombocythemia (ET), (2) early and overt polycythemia vera (PV) and (3) prefibrotic, early fibrotic, and fibrotic chronic idiopathic myelofibrosis (CIMF-0, 1, 2 and 3). Based on established WHO bone marrow features, and the use of new molecular and laboratory markers including JAK2(V617F) mutation, endogenous erythroid colony (EEC) formation and serum erythropoietin (EPO), we present updated European clinical, molecular and pathological (ECMP) criteria for the differential diagnosis of true ET, PV and CIMF. As compared to the WHO bone marrow features, each of the laboratory and molecular markers are not sensitive enough for the diagnosis and classification of the three prefibrotic MPDs. The proposed WHO/ECMP criteria reduce the platelet count to the upper limit of normal (>400x10(9)l(-1)) as inclusion criterion for the diagnosis of thrombocythemia in true ET, early stages of PV and prefibrotic CIMF. The combined use of WHO and ECMP criteria differentiate PV from congenital and acquired erythrocytosis, true ET from reactive thrombocytosis and separates true ET from CIMF-0/1 mimicking ET. Only half of the patients with true ET and CIMF carry the JAK2(V617F) mutation (sensitivity 50%). Early PV mimicking ET is featured by the presence of JAK2(V617F) mutation, EEC, low serum EPO levels, normal hematocrit, and increased bone marrow cellularity due to increased erythropoiesis ("forme fruste" PV) when WHO/ECMP criteria are applied. The combination of JAK2(V617F) PCR test and increased hematocrit is diagnostic for PV (sensitivity 95%, specificity 100%). The degree of JAK2(V617F) positivity of granulocytes is related to disease stage: heterozygous in true ET and early PV and mixed hetero/homozygous to homozygous in overt and advanced PV and CIMF. Bone marrow histology assessment should remain the gold standard criterion for the diagnosis and staging of the MPDs true ET, PV and CIMF and its differentiation from primary or secondary erythrocytosis, reactive thrombocytosis and thrombocythemias associated with atypical MPD, myelodysplastic syndromes, and chronic myeloid leukemia,. The proposed WHO/ECMP criteria allow a cross talk between clinicians, pathologists and scientists to much better characterize the nature and natural history of each of the WHO/CMP defined early and overt MPDs.