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.