52 Greene Street was completed in 1867 by H. J. Howard, who reshaped a row of small commercial buildings into a unified block of fine cast-iron and masonry structures. The land beneath the building was originally part of the West Bayard Farm and, before that, Lenape territory.

Through the late 19th and early 20th centuries, the building housed publishers, silk merchants, and import firms, including J. F. Trow's New York City Directory and the Italian silk house E. Gerli & Co. In 1927 the Lavelli family acquired the building and operated an iron workshop on the ground floor for several decades, with their wrought ironwork commissioned by the New York City Board of Education and by the artists who began moving into SoHo's loft buildings in the postwar years.

A fire in the late 1950s destroyed the top two floors. The Lavellis repaired and modernized what remained but never rebuilt the upper levels. In 1993, the second floor became home to The Painting Center, which exhibited there until relocating to Chelsea in 2010.

The current renovation, undertaken in close cooperation with New York City's Landmarks Preservation Commission, restores the building to its original five-story height, adds a setback penthouse with a green roof, and renovates the cast iron storefront, including the restoration of missing Corinthian leaves and cornices.