By poking high-tech instruments through the wall of one priceless 16th-century mural in Italy, researchers announced Monday that they think they've located the first "encouraging" evidence that a second masterpiece—this one a lost Leonardo da Vinci—is hidden beneath.

Using a tiny camera, the researchers snapped pictures of a telltale hollow space behind Giorgio Vasari's "Battle of Marciano"—and a brick wall—in the Hall of the 500 in the Palazzo Vecchio, Florence's city hall. (Video: 360-degree laser scan of the Hall of 500.)

They also uncovered black pigment and lacquer used in painting—clues that the lost Leonardo may have long ago been saved from destruction.

The findings are inconclusive for now—the Leonardo da Vinci investigation was interrupted by political and public outcry—but they're the first tantalizing leads in a mystery that spans more than four centuries.

The lost work in question is "The Battle of Anghiari" and may stretch more than 20 feet (6 meters) long and 10 feet (3 meters) tall.

According to historical records, Italian statesman Piero Soderini in 1502 commissioned Leonardo da Vinci to paint the scene of Italian knights defeating Milanese forces in 1440 on Tuscany's plain of Anghiari.

Leonardo, it's said, used the opportunity to experiment with a new oil-painting technique, but it ended in failure (five Leonardo da Vinci facts).

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In the 1550s Vasari was hired to remodel the Hall of 500—named after the 500 members of the Republic of Florence's Grand Council—and paint several enormous murals, each dozens of feet high.

One mural was to be painted over Leonardo's unfinished work, but at least one tale describes Vasari as a Leonardo admirer who couldn't bring himself to destroy the work.

Maurizio Seracini, an art diagnostician at the University of California, San Diego, and a National Geographic Society fellow, has searched for clues about the painting for 36 years. (The Society owns National Geographic News.)

"Since the very first day of my research, the goal was to find where 'The Battle of Anghiari' could have been painted ... and if it's still there," Seracini says in an upcoming National Geographic Channel documentary titled Finding the Lost da Vinci. (Video: Preview Finding the Lost da Vinci.)

"I am convinced it's there."

Lost Leonardo: Seek and We Shall Find?

Admiring artists reproduced Leonardo da Vinci's lost mural before its fate was lost in the sands of time (pictures of the Leonardo reproductions)—one of the most famous reproductions of the lost Leonardo being in Paris's Louvre Museum.

Although stunning, the reproductions are not Leonardo's original. The copies almost certainly leave out details lost by shrinking a wall-size mural onto a canvas, and in some cases, it's thought, entire characters have been left out.

As a result, researchers such as Seracini have searched high and low—quite literally—for clues.

A break came in the 1970s, when Seracini climbed a scaffold in front of Vasari's painting and spied two words inscribed in a flag: "cerca trova," which translates to "seek and you shall find." Seracini took it as a cryptic cue that Vasari had built a false wall in front of the Leonardo.

A team led by Seracini eventually got permission to scan the entire Hall of 500 with high-frequency surface-penetrating radar. The scanning revealed some sort of hollow space—only behind the section of mural with the inscription.

To peek behind Vasari's fresco, the team planned to drill 14 strategically located centimeter-wide (half-inch) holes in the work. But an outcry ensued after journalists publicized the project.

"It quickly became very, very political. But they were making little boreholes some 30 to 40 feet (9 to 12 meters) above the ground," said art historian Martin Kemp of the University of Oxford, who wasn't involved in the work.

"In my opinion, that kind of damage can be repaired invisibly."

(See "Lady With a Secret": National Geographic magazine on another potential lost Leonardo.)

Plan B

Despite the public firestorm, National Geographic's Seracini and his team were given a week to continue their work in late 2011—but not in the 14 spots they'd hoped to investigate.

To avoid damaging original portions of Vasari's painting, museum curators permitted Seracini and his team to drill only into existing cracks and recently restored spots.

Many of the locations danced on the periphery of the hollow space, but the researchers struck gold: a hollow space behind 6.7 inches (17 centimeters) of fresco and brick.

They inserted an endoscopic camera into the void and took video of rough masonry work as well as spots that appear to have been stroked by a brush (more on the science of the search for the lost Leonardo da Vinci).

Grit removed from the hole was analyzed with x-rays, and the results suggested it contained traces of black pigment.

Based on the x-ray data, Seracini thinks the black pigments are similar to those found in brown glazes of Leonardo's "Mona Lisa" and "St. John the Baptist." (Read about the struggle to save Leonardo da Vinci's "Mona Lisa" from warping.)

Red flakes also pulled from inside the wall could be lacquer—something that wouldn't be present on a normal plaster wall.

That Seracini found components unique to Renaissance painting leads him to call the work "encouraging evidence," yet he bemoaned the fact that further samples couldn't be collected in the time allotted.

"[U]nless I get hold of a piece of it, and prove that it is real paint, I cannot say anything definite, and that's very frustrating," Seracini says in the documentary.

One of the Most Famous Discoveries of a Century?

Peter Siddons, a physicist at Brookhaven National Laboratory who has verified famous works of art (including a painting by Rembrandt) with particle accelerators, said it seems pretty clear something is behind the Vasari mural.

"There doesn't seem to be enough details out there yet, but based on what has been shared so far, I believe there is a painting. They found paint and they found brushstrokes," Siddons said.

"To jump and say it's a Leonardo da Vinci? That's another question.

"Still, someone took the trouble to build this false wall" he said. "I certainly think that's intriguing."

Oxford's Kemp deemed the results interesting but far from conclusive, since wealthy Renaissance Florentines usually painted their walls for decoration—so the pigments may be from that, not Leonardo's work.

"We can't even be certain which of the long walls Leonardo painted on, as the early accounts are not explicit by any means," he said. "Still, this is a suggestive result at this stage to say, Let's go on a bit further."

Seracini's investigation is on hold again and may not proceed until further political issues in Italy are resolved.

If and when the investigation continues—and if the team recovers evidence of the work—Kemp said it will be one for the record books.

"I think this needs to be resolved. We can't just leave it hanging in the air," Kemp said.