In this second Sherlock Holmes novel, the indomitable sleuth is visited by a woman in distress. Each year for the past six years, on the anniversary of her father's mysterious disappearance ten years ago, Miss Mary Morstan has been receiving pearls, she knows not why or from whom. This time, her anonymous benefactor wants to meet. In the letter, he promises to reveal the mystery and to "right the wrongs" against her. "If you distrust me," he writes,

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The only clue left at the site of a pair of grisly murders is a chicken's foot. Baffled, Inspector Lestrade seeks Sherlock Holmes' assistance in the case.

After Dr. Watson believes he has seen a ghost, Sherlock Holmes is set upon a case that leads to a crime committed in an art museum.

Dr. Watson accidentally leaves a club with another man's coat, a fortuitous occurrence considering the coat proves to be a key piece of evidence after the other man is murdered later that same evening.

Holmes and Watson travel to Sussex to investigate the murder of Squire Douglas, a gentleman who was shot to death in a well-fortified castle, with evidence pointing to only two apparent suspects.

Sherlock Holmes investigates the details behind a strange story conveyed to him by a shopkeeper who claims to have been a member of the League of Red-Headed Men, until it quickly and unexpectedly dissolved.

Dr. John Watson meets private detective Sherlock Holmes and assists him in solving a case that has otherwise confounded Inspector Lestrade of Scotland Yard.

Sherlock Holmes helps one of Dr. Watson's old friends by discovering the source of an odd noise in the man's home, but in doing so, Holmes uncovers a deeper, more serious, mystery.

After Sir Charles Farnsworth is found dead in his castle, a clause inserted into his will firmly requests that his death only be investigated by Sherlock Holmes. Testing reveals traces of arsenic in Farnsworth's body, and suspects abound.

After a boy flees his compartment on a train, he suddenly disappears into thin air. Although his governess believes that he has simply run away, Holmes has other suspicions. Holmes' inquiry into the matter leads him to a nearby circus.