No one knows all the twists and turns Giotto’s “Peruzzi Altarpiece” took as it made its way from Italy in the 14th century to the North Carolina Art Museum hundreds of years later. But its return to Florence leaves nothing to chance.

Museum curators are preparing the five-panel painting for a June 12 exhibition honoring Giotto at the Galleria degli Uffizi, which houses some of Italy’s most prominent art. The painting is rare and somewhat unstable, which concerned museum curators when deciding whether to send the 700-year-old work overseas.

“It was just too compelling a show and such a rare show,” curator Dennis Weller said. “We felt like we just had to do it. It doesn’t mean we’re not scared, but we take all the precautions we can.”

The altarpiece will travel next month in a specially designed microclimate, closed environments that can be as simple as the plastic bonnets that protect works from being touched, to protect it from light, humidity and damage. And a museum employee will accompany the piece the entire route to ensure it safely arrives in Italy.

The “Peruzzi Altarpiece,” donated to the museum in 1960, is one of only a few complete Giotto altarpieces in the world and one of only two Giottos in the United States; the other is at the National Gallery in Washington, D.C.

Curators consider the piece the finest in the North Carolina museum’s collection, and the museum’s chief conservator was shocked when he learned the painting would temporarily leave the museum.

“If we had our way, nothing would travel, everything would stay in storage, in the dark and not be on display,” Bill Brown said. “But we also appreciate that we’re an art museum. ... It’s important for scholarly reason that the painting go to the Uffizi. I have to absorb all that and come up with the best solution to get the painting there safely.”

The good news is that the altarpiece is in fine shape for its age and requires very little restoration. The bad news is that everything about it is hydroscopic, meaning it responds to moisture — the poplar that it’s painted on, the gesso used to prime the panels and the egg tempera used for the paint.

“It makes management of these loans very time-consuming and stressful,” Brown said.

Created in the early 1300s, the painting’s center panel depicts, from the viewer’s left to right, John the Evangelist, the Virgin Mary, Jesus, John the Baptist, and St. Francis of Assisi. The inclusion of these saints provides some of the strongest evidence that the altarpiece was painted for the Petruzzi Chapel, where Giotto painted a series of frescoes — paintings on walls or ceilings — to honor the two St. Johns in 1315. The chapel is dedicated to the two saints.

At some point, the Jesus panel was separated from the other four, not untypical as churches sold paintings for various reasons, sometimes because they needed money. The late Samuel H. Kress, a Pennsylvania businessman whose foundation donated most of the museum’s collection of Italian Renaissance art, reunited all five panels in 1947, and his foundation donated the altarpiece to the museum in 1960.

“This has always been one of those paintings that we’ve said would never leave the building,” Brown said.

Giotto, formally Giotto di Bondone (c. 1267-1337), is considered the father of the western pictorial tradition, moving painting from flat, two-dimensional works with no sense of personality in the figures to three-dimensional works that infused figures with individuality. Painters followed his style until the late 19th century and 20th century, when artists such as Manet once again flattened work and painting became more “art for art’s sake,” Weller said.

Because of his influence and the rarity of his work, the Giotto altarpiece held a place of honor at the entrance of the museum’s Italian galleries. Last month, it was taken down from there and moved to the conservation lab in the museum’s basement, past security guards and behind a door with a keypad lock.

There, it lies flat on a table, where conservator David Beaudin cut a non-glare, UV-filtered form of pricey plastic glass to fit each of the five panels, all of which are just slightly different in size and none of which is square or rectangular. The plastic glass forms the front of the microclimate case.

“Some microclimates are easier to accomplish than others,” Brown said. “This is an extremely challenging one.”

The plastic glass sits in the rabbet, the thin piece of wood inside the frame that holds the painting in place, so each panel sits behind the plastic glass.

The plastic glass, which cost about $1,000 for all five panels, will cover the painting while it’s on exhibit at the Uffizi and, perhaps, once it’s reinstalled at the North Carolina museum.

To finish off the microclimate, Beaudin will use a fancy type of aluminum foil called Marvel Seal to wrap the painting “like giant Jiffy-Pops, basically,” Brown said. That reduces both the air and humidity in the package.

With 21st century technology behind them, the museum will hire an art moving company to take charge of the painting, and send Beaudin with it. Both will make sure the people who run the forklifts in airport warehouses don’t treat a priceless painting as they would a box of electrical components.

“If we don’t distinguish this as valuable cargo and have somebody actually there, an agent from the museum and the art moving company, then it will be treated just like any other cargo,” Brown said.

On the other hand, he said, “We wouldn’t put ’priceless Giotto painting’ on the outside ...”