Former Trump campaign manager Paul Manafort departs from U.S. District Court in Washington, U.S., February 28, 2018.

A breakdown in the cooperation agreement between former Trump campaign chief Paul Manafort and special counsel Robert Mueller suggests prosecutors believe Manafort told them substantial lies, law enforcement experts said.

On Monday, attorneys for Manafort and the special counsel called off a cooperation deal that had been in place since Manafort pleaded guilty to a range of financial crimes in September. The special counsel office said in a court filing that Manafort had lied "on a variety of subject matters" after the deal was struck, and it promised to provide details to the court before Manafort's sentencing.

"It has to be a pretty big deal," said Stephanie Douglas, a 24-year FBI veteran and a former senior official in the bureau's national security branch. "It's not that he lied about the color of a jacket that he wore to a meeting."

In the same joint filing, Manafort's lawyers wrote that the former lobbyist and political operative "believes he has provided truthful information and does not agree with the government's characterization or that he has breached the agreement."

Manafort is one of several Trump associates Mueller has targeted in his probe into possible links between the Trump campaign and the Russian government. The latest allegation could signal a setback for Mueller. Trump's public praise of his erstwhile campaign chief has raised the specter of a possible presidential pardon — a possibility that his lawyers have done little to downplay.

Trump has repeatedly denied any collusion with Russia took place and has labeled the year-and-a-half-long investigation a "witch hunt."

David Weinstein, a defense attorney and former federal prosecutor in the U.S. Attorney's Office in Miami, said that misstating minor facts would be less likely to cause a "significant hangup" for investigators than providing false information that is substantive to the probe.

"That's going to be a bigger problem" for Manafort, Weinstein said. "Not that it's ever the right thing to do to lie, but some lies are more material than others."

The White House did not immediately respond to CNBC's request for comment. A spokesman for the special counsel declined to comment.