Generalized vitiligo is a common, multifactorial, polygenic disease in which autoimmune loss of melanocytes results in depigmented spots of skin, overlying hair, and mucous membranes. In Caucasian families from the United States of America and United Kingdom, susceptibility to generalized vitiligo and associated autoimmune diseases is genetically associated with variants of NALP1, encoding NACHT leucine-rich repeat protein 1. Here, we describe a population-based case-control association analysis of single-nucleotide polymorphisms (SNPs) distributed through the NALP1 region in Caucasian generalized vitiligo patients and controls from Romania. This study confirms genetic association of generalized vitiligo with variation in NALP1, which contains at least two independent risk signals, one tagged by SNP rs6502867 and another tagged by SNPs rs2670660 and rs8182352. Individuals carrying high-risk alleles of both rs6502867 and rs2670660 had an odds ratio of 4.20 compared with individuals carrying a high-risk allele from only one signal. These findings support the involvement of NALP1 in predisposition to generalized vitiligo.