Bone marrow involvement is reported in approximately 25% of patients with newly diagnosed acquired immunodeficiency syndrome-related lymphoma (ARL). Studied were 291 patients with ARL, diagnosed and treated at one medical center between 1984 and 1998. Clinical, immunologic, and pathologic characteristics of patients with bone marrow involvement were compared with those of patients without marrow involvement. Bone marrow involvement was present in 55 patients (19%). Small noncleaved lymphoma was diagnosed in 38% of the entire group and was the most common pathologic subtype in patients with bone marrow involvement (55% versus 34%; P ؍ .008). Analysis of complete blood counts revealed a median hemoglobin level of 10.6 g/dL in both marrow-positive and marrownegative groups. In contrast, a platelet count lower than 100 000/L was more common in patients with bone marrow involvement (27% versus 11%; P ؍ .02). Patients with marrow involvement were more likely to have leptomeningeal (cerebrospinal fluid [CSF]) lymphoma than patients whose marrows were uninvolved (24% versus 7%; P < .001) and were also more likely to have high lactate dehydrogenase (LDH) (P ؍ .002), bone involvement (P < .001), and/or systemic B symptoms including fever, night sweats, and/or weight loss (P ؍ .05). Median survival did not differ between marrow-positive and marrow-negative groups. On multivariate analysis, factors associated with decreased survival of marrow-positive patients included greater than 50% involvement (P ؍ .002), systemic B symptoms (P ؍ .008), and high-grade histologic type (P ؍ .035). Marrow involvement in ARL correlates with small noncleaved pathology, thrombocytopenia lower than 100 000 mm 3 , high LDH, and lymphomatous involvement of the CSF. Survival is statistically shorter in patients with greater than 50% marrow involvement, high-grade pathology, and/or systemic B symptoms. (Blood. 2001;98:2358-2363)