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As her colleagues grilled Stumpf, Warren lit into the head of the nation's second-largest bank, saying reform won't come to the industry until executives are sent to jail.
"This is about accountability," she said. "You should resign, you should give back the money you took while this scam was going on and you should be criminally investigated by both the Department of Justice and the Securities and Exchange Commission."
"The only way that Wall Street will change is if executives face jail time when they preside over massive frauds," she added. "Until then it will be business as usual, and at giant banks like Wells Fargo, that seems to mean cheating as many customers, investors and employees as they possibly can."
As Warren accused Stumpf of "gutless leadership," Wells Fargo's stock price dipped. By midday. it was at $46.20 a share, up 0.43 percent.
Warren's comments came amid testy questioning of Stumpf, who presided over what authorities have labeled as illegal cross-selling to millions of customers who often were enrolled into programs without their knowledge.
She ripped into the culture that created the scandal.
"If one of your tellers took a handful of 20-dollar bills out of the cash drawer, they'd probably be looking at criminal charges for theft," she said. "They could end up in prison, but you squeezed your employees to the breaking point so they could cheat customers and you could drive up the value of hyour stock and put hundreds of millions of dollars in your pocket."
"It wasn't a scam, and cross-selling is a way of deepening relationships," Stumpf said.
Warren, who earned her reputation on Capitol Hill as a crusader for Americans against the financial services industry, is one of the scant few on the Senate banking committee who has not been cut a check by Wells Fargo's political action committee.
—Jon Marino contributed to this report.