Andrés Coca-Pelaz,1 Justin A Bishop,2 Nina Zidar,3 Abbas Agaimy,4 Eloisa Maria Mello Santiago Gebrim,5,6 Vanni Mondin,7 Oded Cohen,8 Primož Strojan,9 Alessandra Rinaldo,10 Ashok R Shaha,11 Remco de Bree,12 Marc Hamoir,13 Antti A Mäkitie,14 Luiz P Kowalski,15 Nabil F Saba,16 Alfio Ferlito17 1Department of Otolaryngology, Hospital Universitario Central de Asturias-University of Oviedo, Instituto de Investigación Sanitaria del Principado de Asturias, IUOPA, CIBERONC, Oviedo (Asturias), Spain; 2Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA; 3Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia; 4Institute of Pathology, Friedrich Alexander University Erlangen-Nürnberg, University Hospital, Erlangen, Germany; 5Otorhinolaryngology Department, National Institute of Rehabilitation, Mexico City, Mexico; 6Radiology Department, Hospital das Clínicas, University of São Paulo, São Paulo, Brazil; 7ENT Clinic, Policlinico Città di Udine, Udine, Italy; 8ARM - Center for Otolaryngology - Head and Neck Surgery and Oncology, Assuta Medical Center, Tel Aviv, Affiliated with Ben Gurion University, Beer Sheva, Israel; 9Department of Radiation Oncology, Institute of Oncology, Ljubljana, Slovenia; 10University of Udine School of Medicine, Udine, Italy; 11Head and Neck Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; 12Department of Head and Neck Surgical Oncology, University Medical Center Utrecht, Utrecht, The NetherlAnds; 13Department of Head and Neck Surgery, UC Louvain, St Luc University Hospital and King Albert II Cancer Institute, Brussels, Belgium; 14Department of Otorhinolaryngology, Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; 15Head and Neck Surgery and Otorhinolaryngology Department, A C Camargo Cancer Center and Department of Head and Neck Surgery, University of São Paulo Medical School, São Paulo, Brazil; 16Department of Hematology and Medical Oncology, The Winship Cancer Institute of Emory University, Atlanta, GA, USA; 17International Head and Neck Scientific Group, Padua, ItalyCorrespondence: Andrés Coca-Pelaz, Department of Otolaryngology, Hospital Universitario Central de Asturias-University of Oviedo, Instituto de Investigación Sanitaria del Principado de Asturias, IUOPA, CIBERONC, Avenida de Roma s/n, Oviedo (Asturias), 33011, Spain, Email acocapelaz@yahoo.esIntroduction: Lymph node metastasis (LNM) from primary tumors of the central nervous system (CNS) is an infrequent condition, and classically it was thought that CNS tumors could not spread via the lymphatic route. Recent discoveries about this route of dissemination make its knowledge necessary for surgeons and pathologists to avoid delays in diagnosis and unnecessary treatments. The aim of this paper is to review the literature and to discuss the relevant pathogenetic mechanism and the cytologic features along with recommendations for surgical treatment of these cervical LNM.Materials and Methods: Using PRISMA guidelines, we conducted a systematic review of the literature published from 1944 to 2021, updating the comprehensive review published in 2010 by our group.Results: Our review includes data of 143 articles obtaining 174 patients with LNM from a primary CNS tumor. The mean age of the patients was 31.9 years (range, 0.1– 87) and there were 61 females (35.1%) and 103 males (59.2%), and in 10 cases (5.7%) the gender was not specified. The more frequent sites of distant metastasis were bones (23%), lungs (11.5%) and non-cervical lymph nodes (11%).Conclusion: Cervical LNM from CNS tumors is infrequent. Pathologic diagnosis can be obtained by fine-needle aspiration cytology in most cases, giving surgeons the option to plan the appropriate surgical treatment. Given the poor prognosis of these cases, the most conservative possible cervical dissection is usually the treatment of choice.Keywords: brain tumors, central nervous system, extraneural metastasis, extracranial metastasis, cervical lymph node metastasis