Thieves broke into the Regional Interdisciplinary Museum of Messina in Sicily late Saturday, removing four wood-panel paintings attributed to the 15th-century Sicilian Renaissance master Antonello da Messina. The theft occurred just before 10 p.m. according to MuMe director Marisa Mercurio, on the Ferragosto national holiday—the feast of the Assumption of Mary and the peak of the Italian summer season.

The stolen works are three of the five surviving panels from the San Gregorio Polyptych, dated 1473, and a double-sided panel depicting the Virgin Mary and the dead Christ in Pietà. The thieves bypassed the museum's alarm and security systems and pried the Pietà panel from an armored display case. Italy's Ministry of Culture confirmed the theft and described all four works as being of "extraordinary value."

The San Gregorio Polyptych has a fragmented history. The painting originally comprised at least five sections and suffered severe damage in the 1908 earthquake that devastated Messina. Only five panels survived; thieves now hold three of them. A comparable Antonello da Messina work, a painting titled "Madonna and Child," is listed on Christie's auction records as having sold for more than $300,000 in 2003.

"We are devastated by what happened. They were two of Antonello da Messina's most important works. It is a tremendous loss for the museum, the city, the community and the art world," Mercurio told the ANSA news agency.

Mercurio's description of "two" works reflects the museum's characterization of the polyptych group and the Pietà panel as the two primary pieces taken—three panels of the polyptych constitute one composite work. The MuMe was closed Sunday while investigators gathered evidence.

Lynda Albertson, chief executive of the ARCA art crimes research association and an art-crime analyst, said the paintings' fame will make them nearly impossible to sell through legitimate channels. "Stealing an Antonello may be far easier than selling one. If these are ordinary thieves, they will soon discover that—to their cost," Albertson told the Italian daily La Repubblica. She said works of this profile frequently move from one criminal network to another, serving as collateral in other illicit transactions rather than being sold outright.

Messina Mayor Federico Basile called the theft a "heinous criminal act" and said he was "deeply outraged," especially because it happened during the city's traditional celebrations honoring the Virgin Mary—the very subject depicted in one of the stolen panels. "We hope that those responsible will be identified and that our artworks will be returned home," Basile said. "Messina will not let its history be stolen."

Culture Minister Alessandro Giuli said the pieces held "extraordinary value for our cultural heritage" and expressed his "dismay and regret" at the loss.

The theft comes months after the Italian state paid $14.9 million for another Antonello da Messina work—a devotional painting titled "Ecce Homo"—at a Sotheby's auction in New York in March. That purchase raised the international profile of the painter and drew renewed attention to his surviving work, the bulk of which remains in and around Messina.

Antonello da Messina is widely credited with introducing Flemish oil-painting techniques to Italian Renaissance art in the late 15th century. His output was small and much of it lost or damaged, making each surviving work rare. The San Gregorio Polyptych represents one of his most significant surviving large-format compositions, and the loss of three of its five remaining panels removes the majority of a work that survived six centuries only to be stripped in a single night.

The theft adds to a recent pattern of high-profile art crime in Italy. Just days before the Messina break-in, police in the northern city of Parma announced the recovery of three stolen works by Pierre-Auguste Renoir, Paul Cézanne and Henri Matisse, collectively valued at roughly 10 million euros, or about $11.5 million. Five people were detained in connection with that theft, which took place March 22-23 at the Magnani Rocca Foundation in the Parma province.

The Carabinieri, whose cultural heritage protection unit—the Comando Carabinieri Tutela Patrimonio Culturale—is one of the world's oldest and most experienced art-crime investigative bodies, was not immediately available for comment Sunday. The investigation is ongoing.