Holmes is approached by Percy Phelps, of the Foreign Office, to recover a document which has been stolen - before it can cause an international scandal and ruin Phelps's career. It seems the British Empire and the Kingdom of Italy have entered into a secret and embarrassing treaty.

An unhappy wife learns that her husband, Colonel Barclay, cheated her earlier fiance, leaving him disabled and in exile. After a fierce argument between them, the Colonel's dead body is found next to his unconscious wife in a locked room with no key, and with curious animal tracks outside the window. Nancy Barclay remains in a coma.Holmes investigates and finds a story of betrayal and a mystery worthy of his powers.

Holmes's brother, Mycroft, seeks his help in deciphering the story a man tells about being kidnapped and forced to translate for an injured Greek. Holmes investigates the disappearance of Paul Kratides, abducted by two villains, Latimer and Kemp, with the aim of forcing him to sign a document releasing his sister Sophie to marry Latimer.

The French government sends for Holmes when the Mona Lisa is stolen from the Louvre. Holmes swiftly decides he is dealing with a mastermind - and none other than his old enemy Professor Moriarty himself.Holmes foils Moriarty's plans to sell Leonardo da Vinci's masterpiece and trails him to Switzerland, where they meet and fight to the death above the famous waterfall at Reichenbach.