Flow cytometry has become an important tool in the diagnosis and characterization of hematologic and lymphoid neoplasia. This technology serves as an excellent complement to microscope-based traditional diagnostic methods and adds distinctive capabilities that are unmatched by any other diagnostic methods. Flow cytometry is ideal for fluids where cells are naturally suspended but is also useful in lymphoid tissues, from which single-cell suspensions can be easily obtained. The advantages of flow cytometry are largely based on its ability to analyze very rapidly, even in small samples, multiple cell properties simultaneously, including size, granularity, surface and intracellular antigens, and DNA content. The quantitative nature of the data produced, both with regard to cell population distributions and to expression of individual cell antigens, offers objective criteria for interpretation of results. Examples of applications include the detection of clonal cells in B-cell lymphoma, the recognition of antigenic expression anomalies in B- or T-cell malignancies, the identification of malignant plasma cells, and the rapid measurement of cell cycle fractions. The unique attributes of flow cytometry allow for increased sensitivity in the detection of neoplastic cells and should contribute to improving accuracy and precision in the diagnosis and classification of lymphomas and lymphoproliferative disorders. Semin Hematol 38:111-123. This is a US government work. There no restrictions on its use.