While Israel has long opposed an Iranian nuclear program, touting a "red line" that cannot be crossed, Mattis also offered his opinion of whether Israel would indeed launch an attack.
"Of course that's the $64,000 question," Mattis said. " ... Do I think Israel will act in its own best interest? Yes. Will they automatically attack? No, it'll be a calculated decision if they do."
If there is a diplomatic agreement reached between the U.S. and Iran, but it does not include limits to the number of nuclear centrifuges and allow U.N. the freedom to inspect the sites, then "we've got a problem," Mattis said.
"To get a deal like that, you've got a bad deal, and that's worse."
In addition to the threat of a nuclear-armed Iran, the former commander of Central Command reasoned that other Arab states such as Saudi Arabia, Qatar, and U.A.E. would build their own nuclear weapons programs in response.
"If the Iranians come away from this with a nuclear program intact, I think there are very bleak options."
"Americans certainly have no appetite for attack," Mattis said, then paraphrasing Winston Churchill's opinion of how the U.S. responds to challenges: "'[But] once the Americans exhaust all possible alternatives, they'll do the right thing."
"Another war in that part of the war would be terrible, Mattis said.
Cautious about "forecasting" exactly what would occur, the general said that economic sanctions and diplomacy can help avoid a war, "but something's got to happen."