A bone marrow (BM) aspiration and biopsy is often believed to be a needed diagnostic procedure in the work-up of patients with fever of unknown origin (FUO), especially in the setting of AIDS. Is it worthwhile to proceed with this invasive diagnostic method? Clinical information obtained on 104 patients in whom AIDS had been previously diagnosed and who had been admitted with a presumptive diagnosis of FUO was retrospectively analyzed. Seventy-two cases met the inclusion criteria. A BM aspiration and biopsy had a low sensitivity as a diagnostic tool even in patients who had abnormal hematologic parameters. BM biopsy was also not helpful in diagnosing non-Hodgkin lymphoma (NHL) cases in this study. Although the incidence of NHL has risen since the emergence of HIV, the predominant types of lymphoma seen in AIDS patients are intermediate/high-grade lymphomas rather than low grade, and consequently, the incidence of BM involvement is low, decreasing the sensitivity of a BM biopsy as a diagnostic tool. These observations were validated in this study. The majority of BM biopsies in this series revealed diagnostic features of infections. This observation can likely be related to the high prevalence of HIV/AIDS patients in this community and opportunistic infections associated with this disease.