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Although the film lists the copyright as Paramount Productions, Inc., copyright records list it as Paramount Publix Corp. Wilson Barrett's play was first performed as one of several productions of a theatrical tour in the U.S. in 1895, which began in St. Louis. It was first seen in England in Leeds the same year and became a sensation when it opened in London on May 27, 1895. Barrett was famous for his portrayal of Marcus Superbus on the stage. Paramount demanded thirty-five percent of the gross receipts from renters for this film.
DeMille made a personal appearance at the Boston premiere and travelled to the east coast on November 14, 1932 to assist in the studio campaign to get this picture through official censor boards without deletions. On December 10, 1932, Motion Picture Herald reported, however, that prior to the film's release, three or four minutes of screen time were cut in which Marcus becomes "the immobile focus of a bombardment of Lesbian wiles offered by a dancing wanton." After early screenings in New York, Motion Picture Herald reported, an "entrancingly sadistic passage limning the approach of a herd of hungry crocodiles waddling to an arena feast of edible, white fleshed Christian girls" was also cut. Motion Picture Herald stated that audiences would love the film "provided their sensibilities survive the odors of Lesbos and de Sade." According to the film's file in the MPAA/PCA Collection at the AMPAS Library, the Hays Office wanted Ancaria's seductive dance around Mercia eliminated entirely. In his autobiography, DeMille recounts the conversation he had with Hays Office director Will H. Hays regarding the scene. After Hays asked DeMille what he was going to do about the scene, DeMille responded, "Not a damn thing." The dance stayed in the picture. A MPPDA memo outlines scenes cut by the Singapore censors, which include: trucks carrying dead bodies, a gorilla dancing around a nude girl and elephants walking over Christians and picking them up with their tusks, all of which were not in the viewed print. In July 1932, Alfred Cohen, president of B'nai Brith of Cincinnati, wrote to Carl E. Millikin of the Hays Office protesting the making of this film, which he claimed was highly offensive to Jewish people. Jason Joy, also of the Hays Office, assured Milliken that there was no basis for Cohen's apprehension concerning anti-semitic propaganda, and the matter apparently was dropped. According to a Film Daily news item on February 27, 1935, a dubbed version of Sign of the Cross opened in Venice, Italy on March 2, 1935. According to Film Daily, this film was the first offering under a contract closed with Paramount by Clement Giglio, an Italian-American impresario, who would henceforth handle Paramount's Italian releases. For his work on the picture, cinematographer Karl Struss received an Academy Award nomination.
Variety reported that during World War II, because of the Allied campaign in Italy, DeMille recommended that this film be re-issued with a prologue uniting the themes of Nero and Adolf Hitler's dictatorships. Prologue production was completed March 25, 1944 and reportedly cost $100,000-125,000. The re-issue came out in 1944, with a prologue lasting 8 1/2-11 minutes, according to various contemporary sources. While Nazi forces occupied Rome, the studio rushed marketing of the re-issue, which was released December 1, 1944. According to a memo in the Code file, the 1944 version received a certificate of approval after a shot of "a robe falling out of scene, presumably leaving [a] woman naked," was deleted. Mitchell Leisen was the art director for the prologue, which was written by Dudley Nichols. The cast for the prologue was as follows: Stanley Ridges (Thomas Lloyd), Arthur Shields (James Costello), Tom Tully (Hoboken), James Millican (Capt. Kevin Driscoll), Oliver Thorndike (Lt. Robert Hammond), William Forrest (Colonel Hugh Mason), John James (Lt. Herb Hanson) and Joel Allen (Bombardier). The prologue takes place in the present of 1944. An American B-17 bomber drops propaganda leaflets over the eternal city to inform Roman citizens that the Allies will be bombing only military stations. As they fly over Rome, two chaplains, a Protestant (Lloyd) and a Catholic (Costello), reminisce about ancient Rome and Nero's persecution of tens of thousands of Christians. Parallels are drawn between Nero and Hitler. The final shot of the prologue is of four planes flying off into the distance. A short epilogue shows the American bombers heading back to North Africa-mission accomplished. In 1944, New York Times reported that there was talk of Paramount re-editing the original Roman bath scene in which Empress Poppaea (Colbert) is immersed in 500 gallons of wild asses milk. In the original version, the cameras caught a glimpse of Colbert's breast as she bathes. In the scene, two kittens are shown drinking from the bath, and press material states that the kittens were added to show the authenticity of the milk bath. By April 2, 1944, it was decided DeMille could keep his bath scene. The New York Times reported on April 2, 1944 that some scenes were omitted from the first version to fit the prologue, but it is unclear which scenes were cut.
In November 1932, Motion Picture Magazine published an article about DeMille "defying the Depression" by hiring 4,500 extras for this film. The article said that half of the Sign of the Cross extras worked with DeMille on The Ten Commandments; and nearly two-thirds on The King of Kings. DeMille reportedly preserved old lists of extras. His casting directors faithfully called every actor on the list before hiring new people. In reference to the hungry actors who hoped for a part in this film, DeMille is reported as having said: "It was heart-breaking...they'd lie in wait for me wherever I went...I don't suppose anyone in Hollywood has heard as many hard-luck stories as I have these last months." Wynne Gibson reportedly walked onto the Sign of the Cross set and DeMille cast her as a lady in audience at the Roman orgy. According to DeMille's autobiography, this film's general release took place during the "Bank Holiday" in the height of the Depression, when every bank in the country was closed in order to prevent a catastrophic collapse of the entire banking system. As a result of a nationwide dearth of cash, DeMille writes, motion picture theater managers accepted "unsecured I.O.U.'s scribbled on little pieces of paper," as admission to this film. Nearly every one of them was redeemed, DeMille reports, when cash began to flow again.
According to a modern source, Mitchell Leisen acted as assistant director and art director on this film, as well as handling costumes, for which he received credit on the viewed print. Modern sources state that John Carradine was in the cast. A British film version of Barrett's play was made in 1904, directed by William Haggar and starring Will Haggar, Jr. and Jenny Linden. Famous Players Film Co. made a film version of the play in 1914, directed by Frederick Thomson and starred William Farnum and Rosina Henley (see AFI Catalog of Feature Films, 1911-20; F1.4006). Paramount re-released the 1932 DeMille version on February 9, 1934 and re-issued it in June 1938. Portions of this film were used in the religious documentary Through the Centuries (see below).