We describe 2 elderly patients with Human herpesvirus 8 (HHV-8)/Kaposi sarcoma herpes virus negative malignant effusion lymphoma showing pan-B-cell immunophenotyping markers and successfully treated with a chimeric anti-CD20 IgG1 monoclonal antibody, rituximab. A 90-year-old man and an 87-year-old woman were hospitalized because of pleural effusions. They were diagnosed as having malignant effusion lymphoma on the basis of cytologic and flow cytometric findings of effusions, revealing involvement of atypical lymphoid cells and expression of CD19 and CD20. The former case was intolerant of chemotherapy because of toxicity. Using the conventional dose of rituximab, they showed neither intolerance nor adverse effects and their pleural effusions decreased immediately. Any sign of disease progression was not noted in either of the patients. They were negative for a HHV-8 infection and had no history of pyothorax. This type of lymphoma was not compatible with primary effusion lymphoma (PEL) defined by World Health Organization Classification of Tumors or pyothorax-associated lymphoma. We diagnosed these patients as having "HHV-8 negative malignant effusion lymphoma". HHV-8 negative malignant effusion lymphoma may be a new clinicopathologic and biologic entity. Because most of the cases were positive for pan-B-cell markers, rituximab may be a promising agent for the treatment.