Purpose Multicentric Castleman disease (MCD) is a distinct lymphoproliferative disorder characterized by inflammatory symptoms, lymphadenopathy, splenomegaly, and cytopenia. Kaposi's sarcoma‐associated herpesvirus (KSHV), also called human herpesvirus‐8 (HHV‐8), is the cause of virtually all cases of MCD occurring in patients with HIV infection. MCD lesions characteristically contain HHV‐8‐infected polyclonal IgMλ plasmablasts. A high frequency of HHV‐8‐related non‐Hodgkin lymphoma has been reported in these patients. Patients and methods We now report on three patients who presented with severe symptoms of MCD, extreme splenomegaly, and rapid expansion of B‐cell lymphocytosis (44–81%) attributable to circulating HHV‐8 positive plasmablasts. Results The circulating plasmablastic cells shared the phenotype (IgMλ, CD19+, CD20− CD138−) of HHV‐8‐infected cells from MCD lesions, mimicking the leukemic phase of large B‐cell lymphoma occurring in HHV‐8‐related MCD. These patients displayed a very high HHV‐8 viral load in blood (>7 logs HHV‐8 DNA copies/ml) and high levels of serum vIL‐6, the viral homolog of human interleukin 6. Serum IL‐6 and IL‐10 were also abnormally elevated. HHV‐8‐infected cells were demonstrated by immunoglobulin gene rearrangement analysis, to be polyclonal and likely represent an expansion of HHV‐8‐infected cells similar to those found in MCD lesions. Conclusion Thus, the spectrum of HHV‐8‐related plasmablastic lymphoproliferative disorders in patients with HIV infection is expanded to include HHV‐8+ polyclonal IgMλ B‐cell lymphocytosis. At onset, this lymphoproliferative disorder may mimic plasmablastic leukemia/lymphoma. Recognizing this unusual complication may have important implications in treatment decision avoiding unnecessary toxicity to the patients.