Peripheral T-cell lymphomas (PTCL) have been difficult to classify. A homogeneous principle of classification is still lacking, partly because lymph node compartments containing functionally distinct T-cell subsets have not been identified. A correlation to differentiated T-cell subsets, as CD4+ or CD8+ cells as well as cytotoxic populations has not revealed clinically meaningful entities. Upon antigen encounter, mature T-cells pass through distinct stages characterized by their surface molecule expression. Naïve T-cells are CD45RA+/CD45R0−/CD27+/CCR7+, however, after antigen contact CD45RA expression is replaced by CD45R0. They differentiate to central memory cells, which retain CD27 and CCR7, or to effector-memory cells, which loose expression of both molecules depending on the strength of the antigen interaction. Immunohistological analysis of PTCL showed an effector or effector-memory cell phenotype (CD45RA−/CD45R0+/CD27−) for both angioimmunoblastic T-cell lymphoma (AILT) and anaplastic large cell lymphoma (ALCL), but different cytotoxic and activation markers expressed by these tumours. A subset of CD4+ PTCL-not otherwise specified (PTCL-NOS) may correspond to a central memory cell phenotype (CD45RA−/CD45R0+/CD27+). Thus, a correlation of PTCL to stages of differentiation, rather than to the direction of differentiation, may reveal homogeneous categories. A comparison between the lymphomas and their normal counterparts maycontribute to the understanding of the underlying transformation mechanisms. Copyright © 2006 John Wiley & Sons, Ltd.