On a stormy night in October 1969, thieves broke into the Oratory of San Lorenzo, a small chapel in what was then Palermo’s dilapidated Kalsa quarter, and made off with one of the city’s artistic masterpieces: Caravaggio’s “Nativity” altarpiece.

Investigators, both national and international, never gave up hunting for the lost painting, which is still No. 2 on the F.B.I.’s list of the top-10 art crimes. Leads pursued in the past all led to dead ends. But new evidence presented at the Oratory this week has revived hopes that the painting might still be found — or, at the very least, that its fate might be discovered.