Background: Diffuse large B-cell lymphoma (DLBCL) in human herpesvirus 8 associated (HHV8+) multicentric Castleman disease (MCD) is a rare type of DLBCL. DLBCL, the most common non-Hodgkin lymphoma, is a cancer arising in the lymphatics. HHV8+ MCD is a lymphoproliferative disorder usually occurring in HIV patients. Patients who develop DLBCL in this setting typically die within a year. Prior National Cancer Database (NCDB) studies have assessed survival and demographics in the broader category of CD20- LBCLs, but have not specifically examined the socioeconomic and demographics associated with DLBCL in HHV8+ MCD. Methods: A retrospective analysis of NCDB data from 2010 – 2020 included patients diagnosed with DLBCL in HHV8+ MCD (N = 237). Demographic factors such as sex, race, Hispanic ethnicity, income status, insurance status, Charlson-Deyo score, facility type/location, and metastasis at diagnosis were evaluated with descriptive statistics. Primary site was also examined. Incidence trends were assessed via regression analysis. Results: A total of 237 patients with DLBCL in HHV8+ MCD were identified in the database, with an average incidence of 21.5 cases per year (R2 = 0.236, SD = 5.7, range = 9 – 29). 74.7% were male and the average age of diagnosis was 53.8 years (SD = 18.62, range = 3 – 90). 40 different primary sites were identified, with the most common being lymph nodes of multiple regions (32.9%). Extranodal primary sites were rare but documented. Charlson-Deyo comorbidity scores varied: Score 0 = 61.6%, Score 1 = 8.4%, Score 2 = 4.2%, Score ≥ 3 = 25.7%. Incidence for race was highest among Whites (69.2%), followed by Blacks (25.3%), then Asians (3.4%). 8.4% of patients were of Hispanic ethnicity. A greater percentage of patients were in the top income quartile (33.8%), compared to the second (19.7%), third (23.9%), and fourth (22.5%). Most patients were either insured privately or by Medicare (73.9%), whereas 8.9% were uninsured. Most were treated at academic facilities (54.7%), and many were treated at facilities in the Eastern United States (47.5%). 19.1% of patients had metastases at diagnosis, most often in distant lymph nodes (6.1%). Conclusions: This study provides insight into the demographics of patients diagnosed with DLBCL in HHV8+ MCD. This cancer showed a nearly 3-fold male preponderance and primarily affected Whites, mirroring existing trends in DLBCL overall. About one fifth of patients presented with metastasis at diagnosis. Interestingly, patient Charlson-Deyo scores displayed a bimodal distribution, with 87.3% of patients having a Score of either 0 or ≥3. The top income quartile was most affected, but patients were more evenly distributed among the bottom three. Further investigation is needed to better define the role of demographics in shaping diagnostic, therapeutic, and outcome discrepancies in those with DLBCL in HHV8+ MCD.