Markopolos, who uncovered evidence that Madoff's wealth management business was a multibillion-dollar Ponzi scheme, said there were typically two types of Ponzi.
There were those that started with criminal intent, such as Madoff's, and those investment schemes which started legitimately enough only to "go rogue" when the market turned against them.
In the latter case, fund managers became too embarrassed to admit their losses.
"So what they do is manufacture or fabricate the returns and end up destroying a lot of lives," he said.
With Madoff - who is serving a 150-year jail term - it was never clear exactly how much money he was managing because of his insistence on absolute secrecy.
From his experience as a fraud investigator, Markopolos said Ponzi scheme fraudsters seemed to have some common personality traits.
"From the cases that I've done, [they exhibit] no remorse, no conscience and no consideration for others.
"They typically treat investors as 'objects of furniture' to be moved around at will."
Commander Stephen Head of the Economic Crime Directorate of the City of London Police said Ponzi scheme operators were often "very compelling" and charismatic.
They also took great care to spread word of their schemes in such a way that aroused as few questions as possible.
Head said Ponzi scheme fraudsters were typically intelligent people who had "tried and tested" means of drawing people in.
In the United Kingdom, some of the most destructive Ponzi schemes had been recommended by family and friends.
Markopolos said investors needed to be wary of returns that looked too good to be true, especially in the present low-return environment.
They needed to be aware of returns that were too steady and seemingly without loss.
He said investors should look for "segregation" between investment management and custody of the assets. They should also double-check financial statements to ensure that instruments had actually traded at the market price.
Markopolos said the cases he had dealt with had tended to be very large.
"Everyone has to have failed to [do] their job - the bankers, the accountants and the due diligence professionals. Everyone has to have failed before they get that big," he said.
"That seems to be the commonality," he said. "And of course the regulators have to miss it all as well."