Abstract Introduction Hematology analyzers occasionally encounter interferences that prevent correct generation of the five-part WBC differential (5PWD). Although the cause of interference is usually unknown, we hypothesized that bilirubin excess drives specific and measurable changes. Methods We retrospectively identified 125 CBC samples run on the Beckman Coulter UniCel DXH800 analyzer (Brea, CA) that yielded an optical scatter pattern that interfered with the differential and had a subsequent 1:2 dilution. Abnormal scatterplots were visually clustered into distinct patterns. The % difference for each component of the differential pre- vs postdilution was calculated for each pattern. Kruskal-Wallis with Dunn’s correction was used to determine whether these changes were significantly different among patterns. Spearman correlation was used to calculate correlation between bilirubin concentration and neutrophil absolute % difference (NAD), a surrogate variable for the magnitude of the interference. Results For 114 (91%) samples, 1:2 dilution resolved interference. We identified four visually distinct optical scatter patterns. The majority showed the hereinafter called type 1 and 2, which yielded the most relevant changes in the 5PWD following dilution and were significantly different from the two other minor patterns. Type 1 (38% of samples) resulted in a NAD of +11.28% (95% CI, +8.93% to +13.63%) and a lymphocyte absolute difference (LAD) of –13.35% (95% CI, –16.16% to –10.54%). The mean bilirubin concentration was 1.45 mg/dL (95% CI, 0.56 to 2.34). Alternatively, type 2 (47%) resulted in a NAD of +25.24% (95% CI, +20.99 to +29.50) and LAD of –26.19 (95% CI, –30.66% to –21.73%). The mean bilirubin concentration was 12.51 mg/dL (95% CI, 9.94 to 15.08), significantly higher than in any other pattern, and with a significant positive correlation with the NAD (r = 0.386; P = .006; NAD = 13.853 + 0.874 * Bili mg/dL). Conclusion Our results suggest that bilirubin produces common and recognizable interference in DXH800 analyzers that responds to dilution, bringing the opportunity to reflexively dilute samples.