Laboratory professionals are in an ideal situation to identify CBC and peripheral blood smear findings that raise the possibility of a hematolymphoid neoplasm, and based on this information make recommendations for additional studies, such as flow cytometric immunophenotyping. In some circumstances a definitive diagnosis can be established from the combined peripheral blood morphologic and immunophenotypic findings obviating the need for bone marrow evaluation, such as for chronic lymphocytic leukemia. Occasionally flow cytometric studies are superior to morphologic assessment, such as in screening for hairy cell leukemia or identifying lymphocytic-variant hypereosinophilia. However, there is increasing recognition of small immunophenotypically unusual or abnormal populations of peripheral blood cells, particularly in older patients, which are of uncertain clinical significance, such as monoclonal B lymphocytosis and T-cell clonopathy. Therefore, it is important to integrate peripheral blood smear review findings with the clinical and other information before recommending flow cytometry. In addition, it is important to recognize situations where the results of peripheral blood smear review and flow cytometric immunophenotyping do not explain the clinical findings.