Sir Arthur Conan Doyle described how he was commissioned to write the story over a dinner with Joseph Marshall Stoddart, managing editor of the American publication Lippincotts Monthly Magazine, at the Langham Hotel in London on 30 August 1889. Stoddart wanted to produce an English version of Lippincott’s with a British editor and British contributors. The dinner was also attended by Oscar Wilde , who eventually contributed The Picture of Dorian Gray to the July 1890 issue. Doyle discussed what he called this "golden evening" in his 1924 Autobiographies/ Memories and Adventures.

The novel first appeared in the February 1890 edition of Lippincott's Monthly Magazine as The Sign of the Four; or The Problem of the Sholtos, appearing in both London and Philadelphia. The British edition of the magazine originally sold for a shilling , and the American for 25 cents. Surviving copies are now worth several thousand dollars.