Human leukocyte antigen (HLA) B27 is the key laboratory parameter for axial spondyloarthritis (axSpA). Its prevalence is variable across different geographic zones and ethnicities, and often mirrors the prevalence of axSpA. HLA-B27 plays a role in axSpA physiopathology. It is correlated with spondyloarthritis phenotype with a consistent positive association with family history, early disease onset, shorter diagnostic delay, hip involvement, and acute anterior uveitis. HLA-B27 has a pivotal role in many referral strategies. However, these strategies were developed in European populations and need to be evaluated in populations with lower HLA-B27 background prevalence, and where additional parameters might be needed.