Introduction In 2015, Sysmex launched a new series of hematology analyzers (XN‐L Series) designed to fulfill the needs of niche laboratories in areas such as pediatrics, dialysis, neurology, and oncology while providing a compact solution. In this study, we evaluate the whole blood and body fluid modes of one of these analyzers, the XN‐350. Methods A total of 300 residual EDTA samples were measured on the XN‐350 in whole blood mode and the XN‐1000 to evaluate method comparison, flagging sensitivity, repeatability, reproducibility, linearity, carryover, and stability. In addition, 191 samples were obtained and processed in body fluid mode which included, cerebrospinal fluid (CSF), continuous ambulatory peritoneal dialysis (CAPD), ascites, synovial, and pleural fluid to perform method comparison, repeatability, reproducibility, linearity, limit of quantitation, and carryover studies. Results Strong agreement was shown between the XN‐350 and XN‐1000 for both whole blood and body fluid modes in results and flagging. Linearity results in both modes on the XN‐350 showed a high R2 value (>.99). For WBC, RBC, HGB, and PLT, the carryover results were well within the predetermined criteria of ≤0.5% for whole blood and ≤0.3% for CSF. Repeatability and reproducibility were acceptable for both modes, and there were no significant deviations present in stability for whole blood. In addition, there was high agreement in all body fluid types evaluated. Conclusion The performance of the XN‐350 is comparable to the XN‐1000 in both whole blood and body fluid modes, making it a reliable alternative to larger analyzers for smaller, niche laboratories.