The falling debris does not appear to have hit or damaged Discovery, which took off on Tuesday on a 12-day mission to the International Space Station, the agency said on Wednesday.
But Nasa said it would launch no more shuttle flights until its engineers could review the problem of debris falling off during blastoff.
Photos taken by Discovery's crew during launch showed that the chunk of foam was missing from the fuel tank, a troubling finding because a 0.75kg piece of foam insulation fell off Columbia's external tank during its launch on 16 January 2003, and hit the ship's wing.
The damage caused Columbia to break apart as it attempted to fly through the atmosphere for landing 16 days later, killing the seven astronauts aboard.
Nasa spent months changing the way foam insulation was applied to the tank and had expected to see only tiny pieces of debris come off Discovery's tank during its launch.
"We won't be able to fly again until the hazard is removed," Bill Parsons, shuttle programme manager, told reporters in a briefing on Wednesday evening. "Obviously we have some more work to do."
"We won't be able to fly again. Obviously we have some more work to do"
Shuttle programme manager
"We think we can make this vehicle safe for the next flight," he said, declining to assess the long-term impact on the manned space programme. "We will determine if it's safe to fly."
Astronauts aboard Discovery were still inspecting their ship for damage on Wednesday while imagery experts on the ground studied thousands of pictures and videos taken during its launch.
Nasa expects to know by Thursday whether engineers want additional inspections with the shuttle's new laser-scanning boom to assure Discovery is in good shape to return to Earth at the end of its 12-day flight.
Preliminary images found that part of a tile, a component of the shuttle's heat shield, also broke off from the area around the shuttle's nosewheel landing gear door.
The mission is Nasa's first manned flight since Columbia. Discovery is scheduled to reach the International Space Station on Thursday to deliver critical supplies.
Atlantis had been scheduled to launch on the next shuttle mission in September, also on a visit to the International Space Station.