Nora Davis, an American tourist, travels to Rome to visit her elderly and unwell aunt, who is under the care of Dr. Marcello Bassi. Unfortunately, Nora’s visit is marred by tragedy as her aunt passes away on the very first night. Feeling responsible and distressed, Nora walks to a nearby hospital to inform Dr. Bassi. However, her ordeal takes a dark turn when she is mugged and knocked out in the bustling Piazza di Spagna. When she regains consciousness, she witnesses a shocking scene: a young woman being murdered right in front of a house. She also observes a bearded man pulling a knife from the victim’s body, which leaves her shaken and confused. Nora soon faints from the shock.
The next morning, Nora wakes up in the hospital and tries to report what she saw to the police. Unfortunately, they dismiss her story, finding no evidence to support her claim that a murder occurred. Despite this, she remains haunted by the incident. At her aunt’s funeral, Nora meets Laura Craven-Torrani, a close friend of her aunt who resides near Piazza di Spagna. Laura, who plans to leave for Switzerland the following day, kindly offers Nora to stay at her house. During her stay, Nora encounters newspaper clippings about a notorious "Alphabet Killer," a serial murderer who has been targeting women in alphabetical order by their last names. The killer has already claimed the lives of three women with last names beginning with "A," "B," and "C." Tragically, Laura’s own sister was one of the victims ten years earlier, murdered right outside Laura’s house.
As Nora tries to make sense of what is happening, she receives a mysterious phone call from an anonymous individual who taunts her with the ominous words that "'D' is for death," hinting that she might be the killer's next victim. Distressed but determined, Nora is assisted by Dr. Bassi, who takes her on sightseeing excursions around Rome to take her mind off her worries. During these outings, they develop a romantic connection, which adds emotional depth to her increasingly tense situation.
One night, after being dropped off home by Marcello, Nora is lured into an empty apartment by a voice transmitted through a tape recorder, warning her that her last name begins with "D." Marcello quickly follows and discovers the apartment is leased to Andrea Landini, an investigative reporter who had been quietly following their movements after spotting Nora in the square. Landini had been working with the police on the case, initially involved in arresting a mentally disturbed man named Straccianeve, who denied being the killer. Landini was committed to proving Straccianeve’s innocence, but his efforts cost him his job.
Curious and suspicious of Landini, Nora begins to investigate further, but their search through Rome’s dark corners yields no concrete clues. Her suspicions deepen when she visits Landini’s apartment, where she uncovers damning evidence—an old confession note on Landini’s typewriter, the tape recorder, and a photograph labeling her as a potential victim. Soon afterward, she finds Landini dead from what appears to be a suicide.
Meanwhile, Laura arrives back in Rome, and Nora learns from the newspapers that a young woman's body has been discovered. At the morgue, Nora is able to positively identify the victim as Straccianeve's daughter, linking the recent murders to the earlier case. That night, she notices something suspicious—the study door is slightly open. Upon entering, she sees a man rising from his chair, whom she recognizes as someone she saw earlier over a body. Before she can react, the man collapses, stabbed in the back. To her horror, she confronts Laura, who reveals herself as the killer. Laura confesses to murdering her sister to claim their father’s inheritance and admits to killing her husband, whom she had stabbed after he tried to have her committed. She reveals that her husband had been disposed of the bodies that Nora had glimpsed earlier. The climax unfolds as Laura attempts to shoot Nora, but she is fatally shot by her dying husband instead.
The story concludes with Nora finding happiness once again as she reunites with Dr. Marcello Bassi, with whom she plans to marry soon, symbolizing her triumphant overcoming of the darkness that had shadowed her through this harrowing ordeal.