Primary effusion lymphoma (PEL) is a rare type of non-Hodgkin lymphoma usually confined to the body cavities of predominantly immunosuppressed patients infected with human herpes virus-8 (HHV-8). In PEL, malignant cells are usually negative for B-cell markers, such as CD19, CD20, and CD79a, but are positive for activation and plasma cell-related markers, such as CD30, CD38, and CD138. It has been reported that HHV-8-unrelated PEL shows high expression of B-cell markers, which is referred to as PEL-like lymphoma. Here, we report two cases of HHV-8-unrelated HIV-negative PEL-like lymphoma in which malignant cells regressed spontaneously after effusion drainage alone. These cells expressed B-cell markers, such as CD20. No chemotherapy was given to either patient, as they were of an advanced age, and both achieved a complete response by effusion drainage alone. One showed a complete response for 16 months after effusion drainage, and the other has survived for 11 months with a complete response. This suggests that sufficient drainage of serous effusion may induce and maintain a complete response in some patients with HHV-8-unrelated HIV-negative PEL-like lymphoma, which represents an excellent treatment option for elderly patients with this disease.