Progress has been made in piecing together the Forma Urbis Romae, a map of Rome carved into stone slabs about AD 210 but later broken into fragments.
Measuring 18m by 14m, it was originally hung in the Templum Pacis, one of the ancient city's major public landmarks.
The map was remarkably accurate but researchers looking for new sites to excavate in Rome had only managed to fit back together a few of the pieces. Now a Stanford University computer program is now being used to aid restoration.
So complicated is the jumble of parts that for decades the map pieces have been referred to as "the biggest jigsaw in the world".
Every few years, a researcher has suggested a match between two pieces. And now, the new computer program produced by Stanford's Dr David Koller has found seven high-probability matches and a host of other possibilities.
"When David put up a slide of his findings at a recent conference there was an audible gasp from the audience," said Professor Marc Levoy, also of Stanford University.
With the new computer analysis, experts are predicting a huge expansion in knowledge of the map and a new insight into ancient Rome.
The Forma Urbis showed almost every feature of the city from the Coliseum and the Circus Maximus, where the chariot races took place, down to individual shops and even staircases. But shortly after the fall of Rome, it is thought that the lower part of the map was torn from the wall, probably to be burned in kilns to make lime for cement.
It may have lain for centuries as just a heap of jumbled fragments, occasionally plundered for other building works.
During the Renaissance, some recognised its importance, but still the pieces continued to be dispersed.
"The map will never be fully recovered; no more than 15% of it survives and that is in 1,186 pieces," Professor Levoy told BBC News Online.
"But there is much about ancient Rome hidden in this jigsaw, and many new computer techniques required to extract it.
"The first big task was to scan and digitise the existing pieces," Professor Levoy said. "In doing so, we have created the largest and most detailed model of a cultural artefact."
The Stanford team has also made its data available to anyone via the internet.
"Anyone can see our 3D models of the map fragments but our software does not allow them to download details of the fragments' geometry."
The need for security regarding the map fragments was dictated by Italian researchers but it is an interesting aspect of the database that Levoy believes may have other uses.
The algorithms developed for matching pieces could perhaps be employed in other areas of science where pattern recognition is required, such as looking for structure within the data obtained by the Human Genome Project.
Town planners and scientists studying urban sprawl may also benefit from the ancient map. The pieces of the Forma Urbis show a mix of monuments, shops, private houses and open spaces which is remarkable given the size of the city at the time. The relationship of private and public spaces has attracted some researchers' interest as a way to tackle town planning today.
But Professor Levoy believes the map will be forever unfinished business.
"With so little of it remaining, we will never match all the pieces we have, but what we can do is gain an insight into unexcavated parts of the city and point archaeologists towards particular sites.
"It's a curious feeling to be walking down a street in Rome and know what was on the same street some 2,000 years before."