Primary effusion lymphoma (PEL) is an aggressive B-cell lymphoma confined to body cavities and universally associated with human herpesvirus type 8 infection. The prognosis of this entity remains poor, with a median survival time of 6 to 9 months. To better understand the clinicopathologic features of the disease and identify possible prognostic factors, we performed a systematic review of the literature for cases of PEL, including 2 previously unreported cases from our institution. PEL was more prevalent in men (92%), with a median age at diagnosis of 55 years. The median overall survival for the entire series was 6 months. Peritoneal involvement (HR:1.62; 95% CI:1.06–2.48) and elevated serum lactate dehydrogenase (LDH) levels (HR:2.50; 95% CI:1.21–5.19) were associated with higher risk of death, while pericardial involvement (HR:0.43; 95% CI:0.20–0.94) was associated with lower risk of death. Therefore, effusion site and serum LDH levels are potential prognostic factors in patients with PEL.