Detection and accurate classification of lymphoid processes in fine-needle aspirate specimens can be a challenging task for the pathologist. Recognizing the usefulness of flow cytometric methods for the diagnosis of lymphoproliferative disorders (LPDs), the authors applied flow cytometric analysis to 38 tissue samples that had a possible diagnosis of LPD and to fine-needle aspiration-derived cytologic preparations. Four aspirations from each sample provided from .44 x 10(6) to more than 70 x 10(6) cells in total. The highest yields were associated with low-grade B-cell non-Hodgkin's lymphomas (NHLs). Washing cytologic preparation cell suspensions did not enhance diagnostic ability and dramatically reduced cell counts (average decrease, 79.8%), potentially problematic with small samples. Comparison of ploidy, S fraction, and immunophenotypic data from the cytologic preparations and cell suspensions made from the conventionally processed parent tissues indicates that cytologic preparation composition closely parallels the tissue of origin. A multiparametric flow cytometric technique used to enhance detection of B-cell clonal expansions allowed for successful recognition of 17 of 21 (81%) B-cell NHLs in cytologic preparations, with false-negative results primarily reflecting a lack of viable tumor cells in the cytologic preparation cell suspensions. A T-cell NHL and a nonhematopoietic malignancy were also identified in cytologic preparations. None of the benign conditions were interpreted as lymphoma. Flow cytometric techniques applied to fine-needle aspirates of lymphoid processes yield important diagnostic information, which may be maximized by adaptations in processing and flow cytometric analysis.