It has been known for a while that T-helper (TH) cells are involved in the regulation of B-cell responses. The characterization of a precise subset of these specialized cells, called follicular T-helper cells (TFH), was first reported in 2000. 1 TFH cells are characterized by their homing capacity in CXCL13-rich areas, such as B-cell follicles, through CXCR5 expression and their ability to support immunoglobulin production. The differentiation and homing of TFH, as well as their interactions with B cells, have been the subject of intense research and several markers have been identified as components of the TFH signature. Thanks to gene expression profiling carried out on peripheral T-cell lymphomas, a TFH signature has been reported in angioimmunoblastic T-cell lymphoma (AITL) and in follicular T-cell lymphoma. 2-4 Several markers that identify TFH cells are now used in hematopathology to reinforce the diagnostic criteria of AITL. In this issue of the Journal, Marafioti et al. 5 describe that inducible T-cell co-stimulatory molecule (ICOS), a CD28 homolog implicated in the regulation of T-cell differentiation and function, appears to be a relevant marker for the diagnosis of TFH-derived lymphoma such as AITL and follicular T-cell lymphoma. This review first summarizes the recent evidence on TFH cell differentiation and the present state of knowledge on molecules expressed by TFH cells. Then, from this perspective, the potential implications of TFH cells in lymphomagenesis and as part of the tumor microenvironment are covered.