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Mammalian immunologists coined primary, secondary and tertiary lymphoid organs based on their developmental, anatomical and functional characteristics and such definitions are often \u201cimposed\u201d on other organisms. For decades, teleost fish were thought to lack lymphoid aggregates beyond those found in the primary lymphoid organs of the thymus and the head\u2010kidney or those found in the spleen (a secondary lymphoid organ). However, over the past two decades several laboratories have uncovered the presence of lymphocyte aggregates in several anatomical locations, mostly mucosal barriers, in teleost fish. These aggregates are difficult to classify as secondary or tertiary lymphoid structures based on the current mammal\u2010based framework. This perspective provides an overview of the latest findings in lymphocyte aggregates in teleost fish and their potential function in adaptive immunity. We proposed a revised definition for tertiary lymphoid organs (TLOs) that is relevant across a wider range of vertebrate taxa and where the lack of baseline SLO makes TLO description and functional characterization even harder. Specifically, we propose experimental paradigms where the \u201cectopic\u201d nature of TLOs could be ascertained in non\u2010model organisms.<\/jats:p>","DOI":"10.1111\/imr.70044","type":"journal-article","created":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T08:48:49Z","timestamp":1750841329000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Is That Lymphocyte Aggregate a Tertiary Lymphoid Organ? Lymphoid Structures in Teleost Fish and the Challenges of Using Mammalian Definitions Across Vertebrate Phylogeny"],"prefix":"10.1111","volume":"332","author":[{"given":"Benjamin J","family":"Garcia","sequence":"first","affiliation":[{"name":"Center for Evolutionary and Theoretical Immunology, Department of Biology University of new Mexico  Albuquerque New Mexico USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4802-6571","authenticated-orcid":false,"given":"Irene","family":"Salinas","sequence":"additional","affiliation":[{"name":"Center for Evolutionary and Theoretical Immunology, Department of Biology University of new Mexico  Albuquerque New Mexico USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,25]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1245704"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dci.2021.104021"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11721-010-0048-2"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12737"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1241680"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxh182"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01751-05"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00244"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-022-04388-x"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112664"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2200396"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2015.07.066"},{"key":"e_1_2_5_14_1","first-page":"267","volume-title":"Advances in Experimental Medicine and Biology","author":"Brown B. 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