The cornea is a transparent structure that permits the refraction of light into the eye. Evidence from a range of studies indicates that central corneal thickness (CCT) is strongly genetically determined. Support for a genetic component comes from data showing significant variation in CCT between different human ethnic groups. Interestingly, these studies also appear to show that skin pigmentation may influence CCT. To validate these observations, we undertook the first analysis of CCT in an oculocutaneous albinism (OCA) and Ugandan cohort, populations with distinct skin pigmentation phenotypes. There was a significant difference in the mean CCT of the OCA, Ugandan and Australian-Caucasian cohorts (Ugandan: 517.3±37 μm; Caucasian: 539.7±32.8 μm, OCA: 563.3±37.2 μm; p<0.001). A meta-analysis of 53 studies investigating the CCT of different ethnic groups was then performed and demonstrated that darker skin pigmentation is associated with a thinner CCT (p<0.001). To further verify these observations, we measured CCT in 13 different inbred mouse strains and found a significant difference between the albino and pigmented strains (p = 0.008). Specific mutations within the melanin synthesis pathway were then investigated in mice for an association with CCT. Significant differences between mutant and wild type strains were seen with the nonagouti (p<0.001), myosin VA (p<0.001), tyrosinase (p = 0.025) and tyrosinase related protein (p = 0.001) genes. These findings provide support for our hypothesis that pigmentation is associated with CCT and identifies pigment-related genes as candidates for developmental determination of a non-pigmented structure.