Helen Stoner needs the great man's help. She lives in a country mansion with her flamboyant and sinister guardian Grimesby Raylott, who has travelled abroad and brought home some souvenir livestock. Recently her sister Julia, about to be married and made by Raylott to sleep in a bed that was screwed to the floor, died in mysterious circumstances. Her final words referred to a "speckled band." Helen is fearful for her own safety and Holmes and Watson investigate.

Sir James Damery, acting for a very illustrious client, consults Holmes. Violet Merville is engaged to marry the Austrian Baron Gruner, who has murdered at least one wife and yet the foolish, headstrong Violet will not hear a word against him. The client is fearful for Violet's safety should the marriage go ahead. Holmes enlists the assistance of Kitty Winter, a woman whom the Baron used and threw aside, to get access to Gruner's album in which he has catalogued his conquests, to make Violet see him in his true light.

Whilst in Cornwall Holmes is approached by the local vicar to determine how Brenda Tregennis died whilst sitting in a room, playing cards with her two brothers, who were struck down with dementia as a result. The trail leads to an African adventurer and a deadly root known as the Devil's Foot.

Miss Violet Hunter has been engaged by the jovial if odd Mr. Rucastle at his country house in Hampshire as a governess to his little boy. The pay is excellent but the terms are bizarre - Miss Hunter has to cut her hair short and stand in the window wearing a blue dress. She realizes that this is for the benefit of a person watching the house continually but needs Holmes' help in working out why.

Red-headed shop-keeper Jabez Wilson comes to Holmes with a puzzle. Goaded on by his young assistant Spaulding, he answered an advert for men with his hair colouring to join the Red-Headed League. It merely consisted of his sitting alone in a room, copying out words for several weeks. One day he found a notice on the door to state that the league had disbanded. What could it mean? Realizing that Wilson's premises are next to a bank and young Spaulding has been digging Holmes is in a position to set a trap to find out.

Holmes is called in by Inspector Hopkins to assist in solving the murder of Sir Eustace Brackenstall, whose house, the Abbey Grange, was also robbed, his young Australian wife Mary, being tied up by the thieves. Evidence points to it being the work of the Randall family, notorious local thieves, but certain discrepancies lead Holmes to rightly suspect a justified crime of passion, made to look like a break-in and a crime whose participants may be allowed to go free.

Why should a wild-eyed Latin go around London, entering shops and burgling houses purely to smash miniature busts of the Emperor Napoleon Bonaparte? Holmes knows. The man is not a lunatic, as the police suspect,but is looking for something concealed in one of the Napoleons.

Mrs. St. Clair is convinced that she momentarily saw her husband, a respectable journalist who commutes to London from their country home, looking out of the window of an opium den in a rough part of the city. The police investigate but find a bundle of clothes and no body. Mr. St. Clair is not dead but Hugh Boone, a literate beggar given to quoting the classics, knows exactly where he is and so - eventually - does Sherlock Holmes.

Mr. Holder, a city banker, is Holmes' latest client. A prominent customer left him a beryl-encrusted coronet as a surety against a loan. Mr. Holder took the coronet home for safekeeping and was shocked to find his son Arthur attempting to deface it. Holmes deduces that Arthur is innocent and was only trying to cover up for another family member who has been duped by a smooth-talking thief.

Holmes' brother Mycroft joins him to investigate the murder of Arthur Cadogan West, a clerk in a government defence office found dead by railway lines with pages from a secret submarine plan in his pocket. Holmes believes that the victim was killed somewhere other than the railway track. Discovering a suspect whose house backed on to the line and could have dropped the body onto a passing train roof leads him towards the culprits who really stole the plans and sought to incriminate an innocent bystander.

Charles Augustus Milverton, 'the most dangerous man in London' is a loathesome blackmailer, preying on the weaknesses of his victims. Lady Eva Blackwell asks Holmes to broker a deal with Milverton to retrieve some letters which would harm her impending marriage but Milverton only ups the asking price. Masquerading as a work-man Holmes discovers where the blackmailer keeps his victims' letters and, with Watson, breaks in at night and destroys them. They are interrupted by Milverton and hide. A woman victim appears and shoots Milverton dead. Holmes makes no attempt to stop her nor will he assist Lestrade in the subsequent murder case.

Josiah Amberley, a retired dealer in artists' materials, engages Holmes to find his wife who has run off with his money and a man called Dr. Ray Ernest whilst he was at the theatre. In the course of his investigation Holmes teams up with rival sleuth Baker, employed by Dr. Ernest's family to locate him. Holmes gets Amberley out of the way and breaks into his house, discovering that things are not as they have been explained to him.

Lady Frances Carfax, an independent aristocratic young woman, goes missing on holiday having dismissed her maid. Watson, later joined by Holmes, investigate a burly follower of the lady but he turns out to be an old flame, Philip Green ,who is anxious to rekindle his acquaintance with Lady Frances. The trail leads back to London and 'Dr. Shlessinger' a jewel thief masquerading as a holy man, from whom Holmes manage to save Lady Frances suffering a macabre fate.