1321 Fifth Avenue was home to a series of medical offices between 1896 and 1921, including Walter F. Edmunson, Carl H. Hitzrot, Myer Gibansky, Milton Goldsmith, Joseph N. Katz, Luba Robin Goldsmith, Simon Ratner, Samuel Lichter, Reuben H. Pearlman, and Irving R. Pearlman.
Through the 1920s, it was home to several Jewish-owned restaurants. Reichbaum’s Restaurant occupied the building from 1923 through 1925, first under the ownership of Abraham Reichbaum and later under Adolph Rapaport. Meyer “Buck” Gefsky of the Coffey Club occupied the building in 1925 and 1926. Abe Brody occupied the building briefly in 1927. Joseph Blau and Mrs. Joseph Klein ran the Little Hungary Restaurant from the location in 1927. The following year, Victor Silverman opened a butcher shop at the location.
From the 1930s through the 1970s, 1321 Fifth Ave. was home to several shoemakers and general stores, including Diamond Shoe Repairing & Hat Cleaner, Jada Novelty Company, Ralph Malorano Leather Company, J. Marcus Company, and the Tri-State Leather Company.