Sherlock Holmes and Henry Vernier are visiting Rome on a diplomatic mission when the Pope asks the world's greatest detective to help find a stolen relic: the forefinger of "doubting" Saint Thomas. But when the relic is quickly and mysteriously returned, and all seems to be easily resolved, the forefinger is stolen again in a brutal attack.

Holmes and Vernier must follow the trail of a sacrilegious murderer through the streets of Rome and the halls of the Vatican, uncovering dark ties between members of the church and an Italian crime family.