The narrator of "The Adventure of the Speckled Band" is John Watson, roommate of Sherlock Holmes, the main character. Holmes is renowned for his investigative skills, and together, the men take on a case brought to them by Helen Stoner. The struggle that Holmes takes on is to try to determine what caused the death of Helen Stoner's twin sister and whether or not Helen is facing a threat to her own life in light of recent similar events at the country home where she lives with her stepfather, Dr. Roylott. Holmes quickly realizes that Helen Stoner has been roughly handled by her stepfather, a man with a violent past and a taste for exotic animals.

The technique that Holmes uses to resolve the question of what killed Helen's sister and whether her life is in danger is his mastery of deductive reasoning. He begins with observation, moves to pattern, to hypothesis, and then to theory. He observes Helen as she tells her story and then travels to Stoke Moran for observation at the scene of the crime. Holmes examines the architecture of the manor home and how the rooms connect. He recognizes the pattern of the sounds that preceded Helen's sister's death. He has witnessed for himself and heard from Helen that Dr. Royloff is given to violence. Holmes's theory that the ventilator in the bedchamber is the route by which something killed Helen's sister is proved on the evening that he and Watson intervene and indirectly cause the death of Dr. Roylott when he makes an attempt on Helen's life with a venomous snake.