The study was based on 271,656 people who had moles recorded during a hospital visit for any medical condition and more than 10 million people who had no such features noted by doctors.
It suggested the former were 4.6 times more likely to develop melanoma - the least common but most dangerous type of skin cancer. The research is being presented at the World Congress on Cancers of the Skin in Edinburgh today.
Study author Dr Eugene Ong, of the Nuffield Department of Population Health, University of Oxford, said: "Our results show that patients with a hospital diagnosis of melanocytic naevi, or moles, have a high risk of developing melanoma both around the site of the mole and elsewhere.
"These people might, therefore, benefit from increased surveillance. Our patients were in hospital or in day-case care when their moles were recorded ... so while this study does not suggest that everyone with a single mole is far more likely to develop melanoma, it does illustrate the link between moles and skin cancer. This is why it is vital people check their moles regularly and report any changes to their doctor."