The story begins when a friend of Dr. Watson's wife comes to Watson's house, frantic because her husband, who is addicted to opium, has gone missing.

Watson is surprised to find that Sherlock Holmes is there too, in disguise and trying to get information to solve a different case about a man who has disappeared. Watson stays to listen to Holmes tell the story of the case of Neville St. Clair.

One day when Mr. St. Clair was in London, Mrs. St. Clair also went to London separately. She happened to pass down Upper Swandam Lane, a "vile alley" near the London docks, where the opium den is. Glancing up, she saw her husband at a second-floor window of the opium den. He vanished from the window immediately, and Mrs. St. Clair was sure that there was something wrong.

She tried to enter the building; but her way was blocked by the opium den's owner, a lascar. She fetched the police, but they did not find Mr. St. Clair. The room behind the window was the lair of a dirty, disfigured beggar, known to the police as Hugh Boone. The police were about to put her story down as a mistake of some kind when Mrs. St. Clair noticed a box of wooden toy bricks that her husband said he would buy for their son. A further search turned up some of St. Clair's clothes. Later, his coat, with the pockets stuffed with hundreds of pennies and halfpennies, was found on the bank of the River Thames, just below the building's back window.