HHV8-positive diffuse large B-cell lymphoma, not otherwise specified (HDN) is a subtype of lymphoma that usually arises in association with HHV8-positive multicentric Castleman disease. However, the epidemiology, treatment patterns, and survival outcomes of HDN are poorly understood. A retrospective analysis was performed for 67 patients with HDN diagnosed from 2011 to 2020 using the SEER database. The demographic characteristics, treatment modalities, and survival outcomes of HDN patients were evaluated. Kaplan-Meier analysis and Cox regression analysis were employed to identify prognostic factors for overall survival (OS) and disease-specific survival (DSS). The age-adjusted incidence rate of HDN was 0.010 per 100,000 person-years. The median age at diagnosis was 51.8 years with male predominance. The primary site distribution was mainly nodal (79.1%), while the extranodal sites were rarely involved (20.9%). The majority of patients were white (65.7%). Only 3.0% of patients received radiotherapy, while 55.2% received chemotherapy. The 1-year, 3-year, and 5-year OS was 67.4%, 65.6%, 58.4%, and 56.3%, respectively, and the corresponding DSS was 73.1%, 73.1%, and 67.8%, respectively. The diagnosis year group of 2016-2020 had a significantly worse OS than the diagnosis year group of 2011-2015 (P = .040), but not for DSS (P = .074). No significant survival improvement was observed in patients underwent chemotherapy. Age and marital status were independent prognostic factors for OS, and age was an independent prognostic factor for DSS. In conclusion, HDN is a rare and aggressive disease, our study provides a comprehensive overview of the epidemiology, treatment patterns and survival outcomes of HDN patients for the first time. We revealed that older age and marital status of single were associated with worse survival of HDN, while chemotherapy was not associated with improved survival outcomes in HDN patients.Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.