Acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) each represent a heterogeneous complex of disorders, which result from diverse mechanisms of leukemogenesis. Modern therapeutic concepts are based on individual risk stratification at diagnosis and during follow-up. For some leukemia subtypes such as AML M3/M3v with t(15;17)/PML-RARA or Philadelphia-positive ALL targeted therapy options are available. Thus, optimal therapeutic conditions are based on exact classification of the acute leukemia subtype at diagnosis and are guided by exact and sensitive quantification of minimal residual disease during complete hematologic remission. Today, a multimodal diagnostic approach combining cytomorphology, multiparameter flow cytometry, chromosome banding analysis, accompanied by diverse fluorescence in situ hybridization techniques, and molecular analyses is needed to meet these requirements. As the diagnostic process becomes more demanding with respect to experience of personnel, time, and costs due to the expansion of methods, algorithms, which guide the diagnostic procedure from basic to more specific methods and which lead finally to a synopsis of the respective results, are essential for modern diagnostics and therapeutic concepts.