A new client, Mary Morstan, engages Sherlock Holmes' services to solve two mysteries: the disappearance of her father, Captain Arthur Morstan, and her receipt of one perfect pearl in the mail each year since answering a newspaper advertisement. But when Holmes' investigation reveals a priceless treasure, the stakes are raised and murder becomes the focus of his inquiry.
The second novel to feature Sherlock Holmes and Dr. John Watson, The Sign of the Four introduces Mary Marston, Watson's future wife.