Acute leukemia and related entities. Impact of new technology. Twenty-seven cases of acute leukemia and related entities were evaluated by morphologic examination, cytochemical study, terminal deoxynucleotidyltransferase study, immunophenotyping, cytogenetic analysis, ultrastructural cytochemical study, and gene rearrangement analysis to determine the impact on the determination of the French-American-British (FAB) classification and the definitive diagnosis. The definitive diagnosis contained prognostic, diagnostic, and treatment information beyond the FAB classification that affected the disease course and patient management. All diagnostic variables were evaluated in each case and were labeled essential, ambivalent, supportive, or noncontributory. Except for gene rearrangement analysis, all variables we studied contributed essential data to establish the definitive diagnosis. Ambivalent findings were rare but could be explained with the knowledge of the total data. All variables, except cytochemical study, whose results were almost always essential, contributed supportive data. Noncontributory data only occurred with cytogenetic analysis in cases that demonstrated normal karyotypes. The FAB classification was established in 20 (74%) of the cases by use of morphologic examination, cytochemical study, and terminal deoxynucleotidyltransferase study. With use of the same variables, however, the definitive diagnosis, whose determination required all data, was established in only 15 (55.5%) of the cases. The addition of immunophenotyping increased the definitive diagnosis to 25 (92.5%) of the cases. The use of ultrastructural myeloperoxidase and platelet peroxidase analysis enabled us to definitively diagnose the remaining two cases (27 cases [100%]). Cytogenetic analysis revealed four cases in which essential information was added to the diagnosis. However, because the cytogenetic information usually was not immediately available, the result did not affect the immediate diagnosis or treatment. Surprisingly, the gene rearrangement studies did not yield essential data in any case and in a few cases contributed ambivalent data. This finding should not exclude gene rearrangement analysis in selected cases; however, the data should always be interpreted in light of all clinical and laboratory findings. This study clearly demonstrates the importance of a multifaceted approach to the understanding of the acute leukemias and related entities and shows the impact of newer technologies on reaching a definitive diagnosis. 