BACKGROUND: Vitamin D has a range of biological effects including antiproliferative functions that are mediated through its receptors, encoded by the VDR gene. OBJECTIVES: We investigated polymorphisms within the VDR gene for association with solar keratosis (SK), a biomarker for skin cancer, and examined interactions with skin phenotype. METHODS: Among participants of the community-based Nambour Skin Cancer Study, we genotyped 190 people with SKs and 190 without for ApaI, TaqI and FokI polymorphisms. RESULTS: We found a significant difference in genotype frequencies of the TaqI polymorphism between affected and unaffected populations (P = 0.008). The TT/tt genotype group was associated with a twofold increase in odds of being affected by one or more SK. Individuals with fair skin and the TT/tt genotype had about a sevenfold increase, whereas fair-skinned people with the Tt genotype had a fourfold increase in odds of being affected by SK. Individuals with the TT/tt genotype who were prone to burn and not tan on acute sun exposure had about a sixfold increase in odds of SK. Fair-skinned people with VDR-Apa AA/aa genotypes had about an eightfold increase in odds of being affected by SK compared with a fivefold increase in individuals with the Aa genotype and fair skin. CONCLUSIONS: The trend for homozygote genotypes to increase the odds of SK suggests that intermediate VDR activity is important in protection or that the heterodimer formed by a heterozygous genotype may have an altered binding potential. Overall, these analyses indicate that VDR may be important in SK development.