Race and ethnicity affect the distribution of molecular alterations seen in patients with non-small cell lung cancer (NSCLC). While anaplastic lymphoma kinase (ALK) alterations are known to occur in 4-5% of the population, data specific to the Hispanic population remains limited. This study describes the real-world incidence of ALK alterations in Hispanic patients with NSCLC treated at a large academic institution in Los Angeles, California, USA to further elucidate the underlying factors that shape differences in mutational profiles. 607 non-small cell lung cancer (NSCLC) patients treated at Los Angeles General Medical Center (n=172) and University of Southern California Norris Comprehensive Cancer Center (n=435) who received comprehensive genomic profiling (CGP) were evaluated from January 2015 to June 2023. Fisher's exact test and multivariate logistic regression were incorporated for statistical analysis. Hispanic patients exhibited a higher incidence of ALK alterations (12.76%, n=18/141) compared to non-Hispanic patients (5.36%, n=23/466) (p=0.0046). Multivariate logistic regression showed Hispanic ethnicity HR 2.393 (95% CI 1.115-5.092) and age at diagnosis HR 0.9325 (95% CI 0.9081-0.9558) were significant variables in ALK alteration incidence. 55.81% (n=24) of ALK alterations were initially found via comprehensive genomic profiling (CGP). This study highlights a significantly higher incidence of ALK alterations among Hispanic patients with NSCLC, emphasizing the impact of race and ethnicity on molecular alterations. Future research is required to evaluate this trend in a larger, more diverse cohort and investigate the roles of environmental factors and tumor microenvironments in influencing ALK alteration prevalence.