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Nolita, derived from "NOrth of Little ITAly", is bounded on the north by Houston Street, on the east by the Bowery, on the south roughly by Broome Street, and on the west by Lafayette Street. It lies east of SoHo, south of NoHo, west of the Lower East Side, and north of Little Italy and Chinatown. Long regarded as part of Little Italy, Nolita has lost much of its recognizable Italian character in recent decades because of the migration of Italian-Americans out of Manhattan. Still, the popular Feast of San Gennaro is held in the area every year on Mulberry Street following Labor Day, on Mulberry Street between Houston and Grand.

The second half of the 1990s saw an influx of professionals seeking Manhattan apartments for rent and an explosion of expensive retail boutiques, trendy restaurants and bars. After unsuccessful attempts to pitch the neighborhood as part of SoHo, real estate promoters and others came up with several different names for this newly upscale neighborhood. Nolita stuck because it follows the portmanteau pattern started by SoHo (South of Houston Street) and TriBeCa (Triangle Below Canal Street). Nolita houses St. Patrick's Old Cathedral at the intersection of Mulberry, Mott and Prince Streets, which opened in 1815 and was rebuilt in 1868 after a fire.  It served as New York City's Roman Catholic cathedral until the new St. Patrick's Cathedral opened on Fifth Avenue in Midtown in 1879. Another landmark is the ornate Puck Building built in 1885 on the corner of Houston and Lafayette Streets, originally the headquarters of the former Puck Magazine.