The Piccadilly Puzzle revolves around the mysterious murder of a woman on a foggy night in a major London thoroughfare. The woman is soon identified as a certain Miss Sarschine, the mistress of a prominent Lord who has just eloped to the Azores on his private yacht with another Lord's wife. Scotland Yard's Detective Dowker, a dour looking and unassuming man, takes on the case, the most difficult of his career. Investigating the aristocracy, lords, ladies, journalists, and using whatever means possible, including a young street urchin, to track this murderer down, is what it will take to stop this murderer from killing again.