The HemoCue WBC DIFF system uses a novel imaging technology to classify total and differential white blood cell (WBC) counts. To evaluate possible effects of ethnical and demographical differences among samples from a US population for this novel imaging technology, the HemoCue WBC DIFF system was compared to the Beckman Coulter LH750, which uses the Coulter Principle to classify differential WBC count. Excellent results were observed on WBC, neutrophils, and lymphocytes with a correlation r = 0.988; y = 1.01 · x − 0.22, r = 0.984; y = 0.98 · x + 0.17, and r = 0.968; y = 0.91 · x + 0.13, respectively. For monocytes, the HemoCue WBC DIFF system measured slightly lower and the correlation for eosinophils was overall good. No impact due to technology could be seen in this study when HemoCue WBC DIFF was compared to one of the state-of-the-art laboratory cell counters.