Such talks could mark a major shift in U.S. policy, which has excluded official talks with Iran for decades.
Rice stopped short of suggesting the countries might reopen diplomatic relations, ruling out any "grand bargain," but she said resolving the nuclear dispute could "begin to change the relationship."
"To underscore our commitment to a diplomatic solution and to enhance the prospects for success, as soon as Iran fully and verifiably suspends its enrichment and reprocessing activities, the United States will come to the table with our EU colleagues and meet with Iran's representatives," she said.
Speaking in Washington today, Rice said the United States acknowledges Iran's right to a civilian nuclear program. But she said Iran must have the full confidence of the international community that it has given up the pursuit of nuclear weapons.
Tehran has denied it intends to produce nuclear weapons.
Rice said Iran faces increased isolation if it continues trying to develop nuclear weapons, but would benefit from improved economic cooperation if it changes course and renews its cooperation with the UN's nuclear watchdog.
Rice also noted that Iran's nuclear program is not the only obstacle in its relations with other countries. She renewed charges that Iran supports terrorist activities and is involved in violence in Iraq.
Bush also spoke briefly about the issue at the White House. He expressed hope that the Tehran government would listen to international demands and it "doesn't foolishly spend money on a weapons program."