Objective: HDAC inhibitors (HDI) are anti-neoplastic drugs with preliminary successful clinical applications in Hodgkin's lymphoma (HL). Systematic investigations of HDAC expression in HL, based on histology and immunohistochemistry are yet rare. Research design/methods: We investigated the expression of HDAC1, 2 and 3 in 283 HL on tissue microarrays. Main outcome measures: Expression of HDAC isoforms was scored in Hodgkin and Reed–Sternberg cells (HRSC) and background infiltrate and compared with freedom of treatment failure (FTF) in 118 cases, for which all data was available. Results: All analyzable HL expressed the HDAC isoforms 2 (n = 194) and 3 (n = 207) in over 50%, mostly 100%, of HRSC and almost all background lymphocytes. HDAC1 was expressed in 169 of 179 analyzable HL in a mean of 82% and in 172 out of 179 analyzable cases in a mean of 83% of infiltrating lymphocytes. HDAC1 of below 75% in HRSC correlated with worse FTF with 16 out of 32 events, compared with 16 out of 82 in cases with over 75% HDAC1-expressing HRSC. Conclusion: HDAC isoforms 1, 2 and 3 are highly expressed in HL. In addition, decreased HDAC1 expression is accompanied by worse outcome in HL.