OBJECTIVES:  To compare how the incidence rates of AML in Australia, Canada and Switzerland differ depending upon the calculation approach taken (detailed bottom up or top down). METHODS:  A comprehensive literature review was undertaken to identify incidence data for AML; this included available databases, registries, clinical trials and research papers. Detailed bottom up studies were reviewed for sample size, date of data collection, breadth of geographic coverage and representation. The incidence of AML has been reported as between 32% - 33% of all leukemia cases, which was applied to a top down calculation using national reported leukemia rates. RESULTS:  For Switzerland, in a bottom up calculation based on data from 128 medical records of adult patients (>16 years) diagnosed with de novo AML during the period 1984-2003, the incidence was 2.6/100,000. Swiss incidence of leukemia was 8/100,000 in 2012, and when the top down calculation rate of 32% (UK proportion) was applied, the incidence was 2.6/100,000. For Australia, the incidence of AML has been reported as 3.4/100,000 in a study from Western Australia for 898 patients diagnosed between 1991-2005. This aligned with the Australian cancer registry reported incidence of 3.8/100,000 (2012). In Canada, 3.7/100,000 people were diagnosed with AML in 2013, falling well below the draft guidelines for orphan designation of 5/10,000 people. In 2012, Canadian total leukemia incidence was 9.5/100,000. Applying the top down calculation based on 33% (US proportion) translated to an AML rate of 3.1/100,000. CONCLUSIONS:  Variation in the incidence rates using a top down or bottom up approach for the three countries ranged between no difference and 0.6/100,000. Across all countries, regardless of approach the AML incidence numbers were well below the incidence rates required for orphan designation. Using both approaches serves to validate the numbers reported.