Although immunophenotyping (IPT) using flow cytometry is a routine technique that is applied in many laboratories as a diagnostic tool for lymphadenopathy, some diagnostic challenges persist. In this review, we will discuss pitfalls in the daily practice of lymph node diagnostics with the focus on general characteristics as lymphoid scatter patterns and lineage specific antigens that are used to define lymphoid populations. The absence of these characteristics on proliferating lymphoid cells can potentially lead to a wrong diagnosis. At the same time, this provides evidence for malignant transformation. Sporadic examples of reactive lymphoid proliferations with similar phenotypes are also discussed, illustrating the need for correlating IPT with morphology and clinical features.