Researchers based at the Dundee University studied DNA shed from melanoma tumour cells into the bloodstream and found a single gene that is "switched off" by the increasingly common cancer.
By monitoring the levels of a chemical known as DNA methylation, which causes the gene to become inactive, they found this "switch-off" correlated with whether or not the cancer had spread around the body.
Early-stage tumours had relatively low levels of DNA methylation, while advanced cancers had much higher levels, suggesting the gene was more tightly shut down.
The results suggest measuring the levels of the gene in DNA in blood could be a useful test to determine whether a patient's melanoma has started to spread and needs additional treatment.
Dr Tim Crook, the study's author and a consultant medical oncologist based at Dundee University, said: "Once melanoma starts to spread it becomes far more difficult to treat. But actually detecting whether or not it has started to spread is also challenging.
"By using a blood test, we have the basis of a simple and accurate way of discovering how advanced the disease is, as well as an early warning sign of whether it has started to spread.
"This would give doctors and patients important information much sooner than is possible at the moment.
"There's increasing evidence that the latest treatments are more effective in these early stages and, if we can identify patients whose cancer has only just started to spread, this would significantly improve the chances of beating the disease."
The study was supported by the London-based Barts hospitals charity, the Brain Tumour Research Charity (BTRC), The Leng Foundation, The Medical Research Council, and Tayside Tissue Bank.
Professor Charlotte Proby, a Cancer Research UK dermatologist based at Dundee University, said: "Using blood tests to assess the landscape of our DNA is a simple way to learn more about what's going on under the skin.
"The switching on and off of certain genes seems to affect when, where and why the melanoma spreads. Our goal is to develop a panel of similar biomarkers that will help us to accurately detect those patients needing extra treatment to fight their melanoma."
Dr Harpal Kumar, chief executive of Cancer Research UK and chairman of the National Cancer Research Institute, said: "Thanks to research, more than eight in 10 people now survive melanoma for at least 10 years.
"But there's still more work to be done to improve things further, particularly for those patients whose cancer has spread to other organs.
"This work could lead to quicker diagnosis and potentially new treatments, giving patients and doctors an even better chance of beating the disease."
Within the UK, Scotland has a higher than average incidence of melanoma, with cases rising by 63% in the decade up to 2010.
About 1200 people are diagnosed with the disease each year, with all age groups affected. More than two Scots aged 15 to 34 are diagnosed with skin cancer each week, making it the second most common cancer in that age range.
Cancer Research UK says the incidence has also risen sharply among the over-50s during the past three decades, with 29 cases of the skin cancer in every 100,000 of the population aged between 50 and 59 in Scotland, compared to about nine per 100,000 in the late 1970s.
Among the victims was Celtic legend Tommy Burns, who died in May 2008 at the age of 51 after a long-running battle with skin cancer.