We measured histone deacetylase (HDAC) activity in 17 patients with primary myelofibrosis (PMF); 19 with other myeloproliferative neoplasm (MPN) and 16 normal volunteers. Significantly elevated HDAC levels were shown in patients with PMF compared with other MPN patients and normal volunteers (p<0.05). Sixteen patients with PMF were also studied for correlation between JAK2 mutation status and HDAC levels; no significant correlation was found. We further correlated HDAC levels with clinical features in PMF: there was no correlation with WBC, platelet counts, Hb levels or degree of bone marrow fibrosis, but HDAC levels were correlated to the degree of splenomegaly. This suggests that HDAC may be recruited as essential thrombocythemia or polycythemia vera progresses into myelofibrosis or PMF progresses into more advanced stage. We then used the qRT-PCR cycle threshold (CT) method to study which HDACs were elevated in PMF. The results showed that, in general, Class 1 HDACs were elevated (HDAC1,2,8) except HDAC3, Class II HDACs were depressed (HDAC4,5) except HDAC6 and 10, and Class III HDACs were generally elevated. The current study may form the basis for using HDAC inhibitor in the treatment of patients with PMF and may implicate a possible role of HDAC in the association of pathogenesis of PMF.