In recent years the literature has described a highly lethal "multicentric" variant of classic Castleman's disease (CD) with similar hyperplastic angio-follicular morphologic features. A 44-year-old man who was not known to be part of any established high-risk group for the acquired immune deficiency syndrome (AIDS) presented with clinical and laboratory features similar to "multicentric" CD. Serologic testing revealed antibody to the human immunodeficiency virus (HIV) by Western blot analysis. It is suggested that "multicentric" CD may be part of the clinicopathologic spectrum of HIV infection, and there should be a high index of suspicion for HIV in patients presenting with generalized lymphadenopathy and histopathologic features of CD.