It is well-established that the absolute neutrophil count (ANC) in many individuals of African and Middle Eastern ancestry is lower than that in White individuals. This lower ANC is associated with homozygosity for a single nucleotide polymorphism (rs2814778) in the promoter region of the Duffy antigen receptor of chemokines (DARC) gene (also called ACKR1, atypical chemokine receptor 1) which confers the Duffy null phenotype [Fy(a−b−)]. This was historically called ‘benign ethnic neutropenia’, but the preferred term is Duffy-null associated neutrophil count, DANC. Several studies indicate that the Duffy-null genotype causes a change in the morphology of neutrophils, facilitating their migration into tissues, thus reducing the number of circulating neutrophils and causing an ‘apparent neutropenia’. Indeed, individuals who have DANC have circulating neutrophil counts that are approximately 2000/uL lower than Duffy non-null individuals, normal bone marrow cellularity and maturation, and a robust response to infections. The Duffy-null genotype is not associated with an increased risk of infection, yet individuals with DANC may experience iatrogenic adverse health outcomes due to their Duffy-null status. This session will be based on cases derived from clinical practice that will highlight the issues that arise from misinterpretation of the ANC in an individual with DANC. With knowledge of this genetic association, normal neutrophil count limits should not be defined by race or ethnicity, but by genetics. Dr. Lauren Merz will discuss the distribution and prevalence of the Duffy null phenotype as well as the selective pressures that likely led to the evolution of this variant. She will describe the physiological impact of this variant on neutrophil behavior and localization. Furthermore, Dr. Merz will review the assessment, development, and implementation of a Duffy null specific ANC reference range. Dr. Mark Sloan will provide an overview of the expected neutrophil count in persons with the Fy(a-b-) phenotype and suggest potential changes to avoid pathologizing healthy individuals. Dr. Sloan will also discuss the clinical implications of the Duffy null phenotype, including its impact on clinical research.