To find the best immunohistochemical marker for megakaryocytes in normal marrow, myelodysplastic syndrome (MDS), and chronic myeloproliferative disorders (CMPD), 57 marrow biopsy specimens were studied semiquantitatively with immunohistochemical methods using a panel of 7 antibodies. The staining intensity was graded 0 to 3 for scoring 100 consecutive megakaryocytes in each stained section. The final score for each stain was the sum of these 100 megakaryocytes individually multiplied by their corresponding grade. In normal marrow (11 cases), the average scores for antivon Willebrand factor (vWF) and Ulex europaeus agglutinin-1 (UEA-1) were 177.1 and 195.1, respectively. The scores for the other 5 markers, including anti-platelet-derived growth factor-BB, 2 anti-transforming growth factor-beta 3, anti-CD61, and anti-CD79a ranged from 96.1 to 124.1. In MDS (27 cases), the scores were 200.8 (vWF), 152.6 (UEA-1), and 28.7 to 98.5 (others). In CMPD (19 cases), the scores were 220.5 (vWF), 179.2 (UAE-1), and 64.8 to 101.2 (others). These results show that vWF and UEA-1 are good immunohistochemical markers for megakaryocytes in normal marrow, and vWF is the best marker in MDS and CMPD. For routine practice, vWF is the most reliable marker for identifying atypical megakaryocytes, especially in the cases of 5q-syndrome and agnogenic myeloid metaplasia.