Thirty-six cases of enterococcal septicemia in patients with hematological malignancies were reviewed retrospectively and categorized according to their clinical significance using strict previously described definitions. Overall, most of the infected patients were males (77%), had acute leukemia (64%), had recently received cytotoxic drug therapy (86%), were granulocytopenic at the onset of septicemia (77%), and acquired the infection during hospitalization (77%). The source of septicemia was unknown in 18 (50%) patients, intestinal in 15 (42%) and intravascular in three (8%). Mortality was 19% among 21 inpatients who had clinically significant septicemia and 30% among patients with septicemia of uncertain clinical significance. The fatal outcome could be definitively attributed to enterococcal septicemia in only one of the nine inpatients who died. Clinically significant septicemia appeared somewhat more frequently to be polymicrobial (p = 0.06), whereas septicemia of unknown significance presented more frequently as breakthrough septicemia (p = 0.013). Unless associated with intravascular infection, enterococcal septicemia in patients with hematological malignancies seems to represent a marker of cytotoxic drug damage of the intestinal mucosa rather than a truly invasive infection.