A novel automated method (Cell-Dyn 3500) allows malaria diagnosis by detecting malaria pigment in white blood cells during routine full blood counts. In Portugal, 174 samples from 148 patients who presented to the emergency department were analyzed. Compared with microscopy the sensitivity was 95% and the specificity was 88%. In 5 cases, false-positive Cell-Dyn 3500 results were from patients who had a recent history of treated malaria, indicating that the method may remain positive during convalescence. Six patients were diagnosed due to the changes observed with the automated method only, because clinicians had not requested malaria smears. This instrument appears to provide a promising method for the diagnosis of malaria, especially where automated full blood counts are routine in the work-up of febrile patients.