Flow cytometry is an invaluable technology in the examination of blood, bone marrow, tissue and body fluids for the presence or absence of hematological disease. It is used in both diagnostic and follow-up testing, with an increasingly important role in the detection of very small residual disease populations (Minimal Residual Disease, MRD) However, flow cytometry immunophenotyping of leukemia and lymphoma is highly dependent on interpretation of results and with the increased complexity of 8-10 color instruments routinely used in clinical laboratories, knowledge of disease-defining populations is increasingly important as is recognizing normal and reactive patterns. This manuscript presents case studies with flow cytometric patterns encountered in routine screening of samples sent for leukemia and lymphoma immunophenotyping, focusing mainly on B-cell disorders which may be missed or incorrectly interpreted by the laboratory (including a hematopathologist) performing the test. Case studies are used to illustrate our laboratory's standardized approach to the interpretation of flow cytometric data. In addition to a standardized approach, these cases emphasize the importance of interpretative skills of technologist and hematopathologists in recognizing abnormal patterns in detecting hematological malignancies.