OBJECTIVES: Cost is an essential part of health economic evaluation. However, no set standard for costing has been suggested/proposed yet, and the impact of using different methods remains unclear. The aim of this study is to compare cost estimates from different costing methods and assess their impacts. METHODS: All adults (>18) newly diagnosed with acute myeloid leukaemia between September 2004 and August 2007 in the Haematological Malignancy Research Network (HMRN, www.hmrn.org, an established UK population-based registry) were included and followed until August 2014. Three costing methods were applied to the treatment pathways. One was a bottom-up costing, for which cost data were obtained directly from treating hospitals; and the other two were top-down costings that used reference costs and tariffs obtained from UK Hospital Episode Statistics (HES). The NHS perspective was adapted and all costs were adjusted to British pounds in 2014 value. RESULTS: The mean survival of 311 AML patients was 1.2 years. The average inpatient costs and standard deviations over a follow-up period ranging from 7 to 10 years were £38,532 (SD: £44,986), £32,115 (SD: £34,293), and £28,662 (SD: £33,298) for bottom-up costing, reference costs, and tariff costings respectively. These differences mainly reflect variations in first-line and second-line treatment costs (p<0.001); while during remission, the cost estimates from the three methods were identical. CONCLUSIONS: This study demonstrates that costing methods can generate substantially different cost estimates. Hence, decision makers need to interpret cost outcomes cautiously, taking account of the assumptions made.