The touching short story "The Last Leaf" by O. Henry takes place during an epidemic of pneumonia in Greenwich Village, New York, around the beginning of the twentieth century. By this time, Greenwich Village had acquired a reputation as an artist's colony and an enclave of alternative cultures. There are several indications that O. Henry was familiar with the area when he wrote the story.

First of all, the author mentions specific locations in Greenwich Village, including Washington Square and Sixth Avenue. He also accurately describes the buildings and streets in the area. For instance, he refers to common features such as "north windows and eighteenth-century gables and Dutch attics and low rents." He describes the ubiquitous brick buildings and the "maze of the narrow and moss-grown" streets. Many of the streets in Greenwich Village are narrow and irregular because the neighborhood, having been already established, was exempted from the modern street pattern of much of the city of New York.

The other indication that O. Henry was familiar with Greenwich Village is in the story's characters, who are struggling artists. Sue and Johnsy are two women, good friends who share an art studio together, and Old Behrman is a failed artist who lives on the ground floor of their building. At the time, Greenwich Village was full of poor struggling artists, and O. Henry captures their characters very realistically.