Multi-parametric flow cytometry is a powerful diagnostic tool that permits rapid assessment of cellular antigen expression to quickly provide immunophenotypic information suitable for disease classification. This chapter describes the classification of B-cell non-Hodgkin lymphoma (B-NHL) by flow cytometry suitable for the clinical and research environment. In addition to describing the immunophenotypic patterns of the most common B-NHL (including examples of common B-NHL), the effect of anti-CD19, -CD20, and -CD38 therapies on the evaluation of flow cytometric data is also discussed. Over the last 15 years, our laboratory has developed flow cytometry combinations that can immunophenotype classic Hodgkin lymphoma (CHL), nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), and T-cell/histocyte-rich large B-cell lymphoma (THRLBCL) and the use of these assays will be presented. The CHL assay combination is also particularly well suited to immunophenotype primary mediastinal large B-cell lymphoma (PMLBCL) and our experience immunophenotyping PMLBCL by flow cytometry will be discussed. Finally, an approach to the evaluation of the reactive infiltrate of CHL, NLPHL, and THRLBCL that can provide diagnostic information will also be provided.