Hemophagocytic syndrome (HPS) is a reactive process that complicates several diseases including hematological neoplasias (HN). It has been suggested that HPS may be a negative prognosis factor for neoplastic diseases. In this retrospective analysis, 13 cases with HPS associated to HN were compared with two age, sex, diagnosis, disease stage and treatment matched controls in order to determine the impact of this syndrome on the survival. Cases with HPS were adult patients with a male:female ratio of 1:1 and their clinical picture was characterized by fever, lymphadenopathy, hepatosplenomegaly, and pancytopenia. Median survival since HN diagnosis was 7 and 48 months for the HPS and control groups, respectively (P = 0.0001). In ten patients who died, median survival after HPS presentation was 1 month. These results suggest that the presence of HPS is a negative prognosis factor in patients with HN. Due to its high mortality rate, an individualized, early, and intensive chemotherapeutic regimen may be required for HN complicated with this syndrome.