"The Adventure of the Speckled Band" begins in the familiar setting of 221B Baker Street in London, where so many of the Sherlock Holmes stories begin and end. It is still a time when Watson is sharing a set of rooms with Holmes, but they both get fully dressed and go downstairs to the parlor when the desperate and terrified Helen Stoner calls on Holmes in the early morning. In those Victorian times it would have been improper for a young woman to visit Holmes in his flat. After Helen tells her background story and leaves, Dr. Roylott bursts into Holmes and Watson's rooms and threatens them with bodily harm if they interfere in his affairs.
The story moves to the main setting, which is the ancient, rambling house called Stoke Moran, in the country a short distance from London. It is a spooky, Gothic-type of place which is so badly decayed and neglected that only part of the house is still habitable. The few acres around it are overgrown, and two wild animals prowl the grounds at night--a cheetah and a baboon. Watson describes the place in some detail when he and Holmes go there to investigate Helen Stoner's problems and perhaps protect her from the same fate that befell her sister Julia.
The building was of grey, lichen-blotched stone, with a high central portion and two curving wings, like the claws of a crab, thrown out on each side. In one of these wings the windows were broken and blocked with wooden boards, while the roof was partly caved in, a picture of ruin. The central portion was in little better repair, but the right-hand block was comparatively modern, and the blinds in the windows, with the blue smoke curling up from the chimneys, showed that this was where the family resided. Some scaffolding had been erected against the end wall, and the stonework had been broken into, but there were no signs of any workmen at the moment of our visit.
Most of the important action takes place in two of the three adjacent bedrooms: the room currently occupied by Miss Stoner and the bedroom of the half-mad and violent Dr. Roylott, her stepfather. His room interests Holmes because of the safe, the saucer of milk, and the dog leash with a loop at the end. His stepdaughter's room interests Holmes because of the ventilator, the dummy bell-rope, and the fact that the bed has been bolted to the floor so that it cannot be moved. Helen is staying in the room where her sister was murdered because Roylott has ordered some unnecessary repairs on Helen's own bedroom in order to force her to move into the one next to his, where he plans to cause her death by having his deadly swamp adder ("the speckled band") crawl through the ventilator, slither down the bell-rope, and drop onto her bed.
The story concludes back at Holmes and Watson's room at 221B Baker Street, where Holmes explains all his observations, theories and deductions to his friend. They have one big sitting room and two separate adjoining bedrooms on the second floor. Mrs. Hudson, their landlady, serves their meals on a big table in the sitting room.