US Secretary of State Condoleezza Rice says she does not rule out a meeting with her Iranian counterpart at a conference on Iraq's security in Egypt.
Ms Rice said any meeting with Iran would focus on Iraq only
The summit next week will bring together Iraq's neighbours and other regional and international powers.
But Ms Rice said Iraq would be the only topic of any talks with her Iranian counterpart Manouchehr Mottaki.
The US has accused Iran of helping insurgents in Iraq, a charge Iran has strongly denied.
Ms Rice's comments exclude the possibility of talks on Tehran's controversial nuclear programme.
Washington does not have diplomatic ties with Tehran, but envoys did meet at a conference on Iraq in March.
Ms Rice said any "encounter" with Iran would be a chance to discuss Iraq's security situation, and not specific US-Iranian relations.
"This is not a meeting about the United States and Iran," she told ABC's This Week programme.
"This is a meeting about Iraq and about what Iraq's neighbours and interested parties can do to help stabilise the situation in Iraq."
Nevertheless, if this US-Iranian encounter were to happen it would mark a significant breakthrough, the BBC's Iranian affairs analyst Pam O'Toole says.
And if such talks went well, she says, they could pave the way for discussions on wider issues in the future.
The US has not had diplomatic relations with Tehran since the 1979 Iranian revolution.
On Sunday, Tehran finally confirmed that would attend the Sharm el-Sheikh conference on 3-4 May.
Iran had been reluctant to go because it would mean engaging with the US, the BBC's Frances Harrison in Tehran says.
It was also unhappy by the decision to expand the summit to include not just Iraq's neighbours but also the five permanent UN Security Council members and other Arab nations.
Security operations are continuing across Iraq
In addition, there were also some in Iran who tried to link attendance to the fate of five Iranian detainees in US custody in Baghdad, our correspondent says.
But Tehran later said the two issues were not connected.
Iraqi Foreign Minister Hoshyar Zebari welcomed the prospect of talks between Iran and the US.
"I think it's important, it would be a major breakthrough and any reduction in tensions will positively impact the situation in Iraq," he said.
"We don't want Iraq to be a battleground for settling scores on other agendas at our cost. Really, this has been harming us, damaging us a lot."
Iran has close ties with Shias in Iraq, and has been accused by the Washington of arming and training Shia militants for sectarian conflict with Sunnis.
The diplomatic moves come as US-led forces continue a security crackdown in Iraq.
On Sunday night, the US carried out what it called a massive effort to disrupt the networks of al-Qaeda in the country.
The US said 72 suspected militants had been detained in raids west and north of Baghdad, in the provinces of Anbar and Salahuddin.