The prevalence of cutaneous malignant melanoma (CMM) has increased significantly in most Caucasian populations in recent decades. Both genetic and environmental risk factors are involved in the development of CMM. A germline mutation in the syntaxin 17 (STX17) gene of horses was recently identified, which causes premature hair graying and is associated with susceptibility to melanoma. We hypothesized that common germline variants in the STX17 gene might be associated with a predisposition to human CMM or might interact with other melanoma risk genes. We genotyped 26 tagging single nucleotide polymorphisms (SNPs) across the STX17 gene region in an Australian sample of 1560 melanoma cases and 1650 controls and performed logistic regression analysis to identify potential SNP interactions in a combined dataset. Our results do not support an association between CMM and any of the STX17 SNPs and provide no evidence for interactions between the melanoma risk SNP rs910873 on chromosome 20 and any of the STX17 SNPs. We conclude that common variants in the STX17 gene region do not play a key role in the pathogenesis of human melanoma.