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Dick Tracy's foe for this serial is the crime boss and Masked Mystery Villain The Spider/The Lame One and his Spider Ring. In the process of various crimes, including using his Flying wing and sound weapon to destroy the Bay Bridge in San Francisco and stealing an experimental "Speed Plane", the Spider captures Dick Tracy's brother, Gordon. The Spider's minion, Dr. Moloch, performs a brain operation on Gordon Tracy to turn him evil, making him secretly part of the Spider Ring and so turning brother against brother.
Dick Tracy battles spies and saboteurs in his efforts to bring to justice the Stark gang, a criminal family led by the vicious Pa Stark.
A mad doctor named Zanoff uses a drug to bring himself back from the dead after his execution in prison. Dick Tracy sets out to capture Zanoff before he can put his criminal gang back together again.
Dick Tracy goes up against a villain known as The Ghost, who can turn himself invisible.
Dick is faced with a series of brutal murders in which the victims, all from different social and economic backgrounds, are viciously slashed to pieces. Suspects abound but Tracy, getting a clue that there will be 15 murders in all, must find the common thread among the victims before more are killed.
A police detective uses his girlfriend to track down a homicidal maniac.
Dick Tracy investigates the theft of a fortune of fur coats, a possible insurance swindle and several murders, all linked to a huge thug who wears a hook in place of his right hand.
A gang of criminals, which includes a piano player and an imposing former convict known as 'Gruesome', has found out about a scientist's secret formula for a gas that temporarily paralyzes anyone who breathes it. When Gruesome accidentally inhales some of the gas and passes out, the police think he is dead and take him to the morgue, where he later revives and escapes. This puzzling incident attracts the interest of Dick Tracy, and when the criminals later use the gas to rob a bank, Tracy realizes that he must devote his entire attention to stopping them.