Prostate cancer is the third most common cancer in men and the second largest killer behind lung cancer. The beneficial effect of ultraviolet radiation (UVR) on the development of certain internal cancers including the prostate has previously been shown. Epidemiological studies in the USA showed a link between latitude and prostate cancer mortality and this led to confirmation of a protective effect of UVR in the development of prostate cancer in a small group of 210 cancer patients recruited in North Staffordshire, UK between 1999 and 2000. In this study, we confirmed this association in a further group of 243 independently recruited prostate cancer patients. We also showed that various parameters of UVR exposure have an increased protective effect in the development of the disease in combination compared with individually. Skin type was also found to be a risk factor in prostate cancer development especially in men with low levels of UVR exposure. The mechanism for this protective effect is postulated to involve vitamin D via the interaction of UVR exposure on the skin. Polymorphisms in genes associated with skin pigmentation (tyrosinase) and vitamin D (vitamin D receptor, vascular endothelial growth factor) were also shown to be significantly associated with prostate cancer risk, again, especially when patients were stratified by UVR exposure. These findings provide further evidence that the mechanism behind the UVR effect involves vitamin D. The level of UVR that is needed to obtain this benefit needs to be ascertained as it is well known that too much exposure to UVR increases individual risk of developing skin cancer. Accordingly, these findings may eventually have major public health implications.