The occurrence of false-positive blood cultures in patients with acute myeloid leukemia has been rarely described in the literature. Awareness of this finding is important to avoid unnecessary delays in initiating appropriate cytoreductive therapy. Here, we present the case of a 70-year-old male with acute leukemia and persistently positive blood cultures despite broad-spectrum antibiotic therapy. No source of infection could be found clinically, and no pathogen could be isolated from blood cultures. Inspection of the CO2 plots of the positive blood cultures showed a steady linear increase in CO2 levels, suggesting false-positive detection by the automated microbial detection system. Cytoreductive therapy was then initiated, and several subsequent blood cultures were negative.