The World Health Organization's Classification of Tumours of Haematopoietic and Lymphoid Tissues (Swerdlow et al. (eds) WHO Classification of tumours of haematopoietic and lymphoid tissues, 4th edn. WHO Press, Lyon, 2008) created a classification scheme incorporating genetic, molecular, morphologic, and immunophenotypic characteristics. The diagnosis of acute myeloid leukemia requires equal to or greater than 20% blasts (except in some cases with specific cytogenetic abnormalities or in erythroleukemia). The diagnostic work up typically includes morphologic, cytochemical, and immunophenotypic features. This generally includes evaluation of the peripheral blood, bone marrow aspirate, and bone marrow trephine biopsy. As stated in the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, "the contribution of an adequate bone marrow biopsy cannot be over stated" (Swerdlow et al. (eds) WHO Classification of tumours of haematopoietic and lymphoid tissues, 4th edn. WHO Press, Lyon, 2008). The evaluation of the bone marrow biopsy provided the necessary material for immunohistochemical studies used for both diagnosis and prognosis.The following text will focus on the utilization of immunohistochemical studies in the classification of acute myeloid leukemia. Other methodologies will be discussed elsewhere in this volume.