Generalized vitiligo (GV) is characterized by autoimmune destruction of melanocytes by skin-homing cytotoxic T-cells (CTLs) that target melanocyte autoantigens. Two recent genomewide association studies (GWAS) of GV in European-derived whites (EUR) have demonstrated genetic association with GZMB, encoding granzyme B, a marker of activated CTLs that mediates target-cell apoptosis, as well as autoantigen activation and consequent initiation and propagation of autoimmunity. Here, we describe detailed genetic analyses of the GZMB region of chromosome 14q12 to identify genetic variation potentially causal for GV, implicating two non-synonymous SNPs in strong linkage disequilibrium that comprise part of a common multi-variant high-risk haplotype, rs8192917-C— rs11539752-C (55R-94A). To identify possible uncommon deleterious variants that might “hitchhike” on the high-risk haplotype, we then carried out “next-generation” DNA re-sequencing of GZMB in 114 EUR GV patients. Overall, our findings support a direct causal role for the GZMB rs8192917-C—rs11539752-C haplotype (55R-94A) in the pathogenesis of GV.