Background: This study aims to evaluate the trueness of the DI‐60 Digital Cell Imaging Analyzer on Wright‐stained samples with a focus on prevalence‐dependent quality indicators for differential blood counts requested from non‐hematology wards. Methods: Two hundred and ninety‐nine samples were included into this performance evaluation study at the Department of Laboratory Medicine, Medical University of Vienna. The following aspects were verified: (a) the reliability of automatedly pre‐classified differential counts, (b) the concordance of DI‐60 counts with manual‐microscopic differential counts and (c) the agreement of DI‐60 and manual‐microscopic results regarding clinically relevant findings. Results: 82.3% of all leukocytes were correctly pre‐classified. Cell categories with a low prevalence (eosinophils, basophils, progenitors/precursors) in non‐hematological patients presented with a low positive predictive value (PPV), indicating a high frequency of false positives. Comparisons between visually adjusted results of the DI‐60 and manual‐microscopic differential counts revealed a good concordance for neutrophil and lymphocyte counts. Besides the detection of precursors/progenitors and normoblasts, no relevant systemic errors were detected. However, due to their low prevalence and technical aspects, the detection of basophilia, monocytosis or the presence of precursors/progenitors showed comparably low accuracies (error rates of 7.4%–24.1%). Conclusion: The DI‐60 system works well for Wright‐stained samples collected in the non‐hematology ward. Due to the varying prevalence of cell categories found in peripheral blood, a low PPV can be expected with automatic assignment for those cells with low prevalence (e.g., basophils, eosinophils, precursor and progenitor cells, plasma cells). If the pre‐test probability of these conditions is increased, manual microscopic processing may be recommended. [ABSTRACT FROM AUTHOR]