We retrospectively analyzed 45 cases of HIV-associated Hodgkin lymphoma (HIV-HL). HIV-HL generally is a disease of young white men (mean age, 40.1 years) who acquired HIV infection by homosexual or bisexual behavior (68%), intravenous drug use (24%), and/or blood transfusion (8%). The mean interval between the diagnosis of HIV and HIV-HL was 5.2 years. Morphologic classification of nodal biopsy specimens (2001 World Health Organization criteria) included 15 mixed cellularity Hodgkin lymphomas (MCHLs), 14 nodular sclerosis Hodgkin lymphomas (NSHLs), 9 lymphocyte depleted Hodgkin lymphomas (LDHLs), and 7 classic Hodgkin lymphomas, type not further categorized. The Hodgkin-Reed-Sternberg (HRS) cells expressed positive immunoreactivity with fascin (30/30 [100%]), CD30 (35/37 [95%]), CD15 (32/36 [89%]), bcl-X(L) (25/31 [81%]), bcl-2 (15/29 [52%]), CD20 (4/34 [12%]), bcl-6 (3/28 [11%]), and Epstein-Barr virus latent membrane protein-1 (32/33 [97%]) and were nonreactive for CD138/syndecan-1. CD4 and CD8 immunostaining showed an inverted CD4/CD8 ratio (<1/20) in all cases. At diagnosis, most patients (n = 27) had high-stage disease (IV(E)) associated with an aggressive course (16% 5-year survival). LDHL behaved more aggressively than MCHL and NSHL (15% vs 40%, 5-year survival, respectively), as did disease with a sarcomatoid pattern (11% 5-year survival). Chemotherapy and radiotherapy proved efficacious in a minority of these patients.