Major Sholto, a retired British army officer, who has amassed wealth in India in a mysterious manner, dies suddenly. His two sons were unable to find any trace of the wealth. Search the house patiently, and at last in an attic, concealed by a secret panel, discovered a brass bound box. It contains jewels of almost fabulous value and a letter, telling them that Mary Morstan, the orphan daughter of one of Sholto's brother officers in India was entitled to an equal share in the treasure. Thaddeus, the younger brother, is willing to carry out his dead father's wishes, but Bartholomew, the elder, insists that they alone should possess the jewels. Finally Thaddeus, unable to persuade his brother to relent, writes Miss Morstan an anonymous letter, telling her that she has been wronged, and naming the place where they can meet. Miss Morstan, perplexed by the strange communication, consults Sherlock Holmes. Holmes and Dr. Watson, his associate, keep the appointment with Miss Morstan and are led by Thaddeus Sholto to his home. Thaddeus tells Miss Morstan of her inheritance, and that he intends to force his brother Bartholomew to surrender her share of the treasure. They reach the Sholto mansion, and Thaddeus goes to his brother's room to summon him. But he comes dashing downstairs, terror stricken. Holmes and Watson dash up the stairs, leading to the room. There, huddled in his chair, is Bartholomew and on his breast a torn sheet of paper, with five words scrawled upon it, "The Sign of the Four." The treasure is gone. A quick examination shows that the man has been killed by a poisoned thorn which is lodged in his head. In the garret Holmes comes upon fresh evidence of intruders. In the heavy dust are impressions of a boot and of a wooden leg, and the imprint of two little bare feet. The detective hurries to the roof, where, dangling to the ground below, is a heavy rope. Securing a bloodhound he tracks the fugitives down, the chase finally leading him and his coworker, Dr. Watson, to a little ship-yard, where he learned that a man with a wooden leg, accompanied by a little East Indian, had hired a motorboat and sailed up the river. Holmes, in another boat pursues. The fugitives are captured, but not before they throw the treasure overboard. Then Jonathan Small the man with the wooden leg, and his faithful follower, little Tonga, whose deadly blow pipe had killed Sholto, are brought to Holmes' rooms and the casket opened. The jewels are not there. The treasure had disappeared forever.