"Mona Lisa" was the first song not performed in English to win an Oscar for Best Song. Amazingly, it was more than fifty years before another foreign language composition took the gold. As of 2020, only two songs have accomplished the feat: "Al Otro Lado Del Rio" from The Motorcycle Diaries (2004) and "Jai Ho" from Slumdog Millionaire (2008).

Composer Hugo Friedhofer subtlely weaves the opening notes of "Mona Lisa" into his background score, but the song does not appear in the main title or end credits of the film and is never sung in English. Its only presentation is in the wartime sequence at the film's start, informally warbled in Italian by a soldier standing guard while accompanying himself on guitar, purely as a covert means of warning his fellow soldiers that danger is imminent.

Although set in post-war Italy and featuring an important local Italian family, none of the 5 featured actors is Italian. Joseph Calleia (Dr. Lunati) is Maltese; Richard Avonde (Carlo) is Canadian, Celia Lovsky (Contessa) and Francis Lederer (Baron Rocco) were born in what was Austria-Hungary; and Wanda Hendrix (Baronessa Giulia) is from Jacksonville, FL.

"Mona Lisa" was initially written off as a dark horse for winning the Best Song Oscar, as no composition from a non-musical picture had ever accomplished the feat. At the time, the song was considered a throwaway moment in Captain Carey, U.S.A. (1950) that lassoed a nod only because 1950 was a slow year for musicals. Paramount obviously did not conceive of a nomination, as the song didn't even receive a screen credit for its composers, Ray Evans and Jay Livingston. On the evening of the awards, "Mona Lisa"'s win was a genuine upset, beating out "Be My Love" from The Toast of New Orleans (1950), "Bibbidi-Bobbidi-Boo" from Walt Disney's Cinderella (1950), "Mule Train" from Singing Guns (1950) and "Wilhelmina" from Wabash Avenue (1950).

There had been numerous Best Song nominations from non-musical pictures since the advent of the category in 1934, but "Mona Lisa" was the first of these to actually win the Academy Award. Captain Carey, U.S.A. (1950) did not hold the distinction for long. In fact, it broke the lock musicals had had on the category until that time. Just two years later, High Noon (1952) repeated the feat, quickly followed by Three Coins in the Fountain (1954), Love is a Many-Splendored Thing (1955), The Man Who Knew Too Much (1956), The Joker is Wild (1957) and A Hole in the Head (1959). By the 1960s, with musicals now out of vogue, it became commonplace for a drama or comedy to win Best Song, with only two statuettes going to musicals: Mary Poppins (1964) and Doctor Dolittle (1967). In the decades that followed, only five musicals scored gold: Nashville (1975), A Star is Born (1976), Thank God It's Friday (1978), Fame (1980) and Flashdance (1983). Not until Disney returned to making animated features in 1989 did musicals once again become serious contenders for a Best Song Oscar.