The honeymoon was over when Cream left in the night for England, leaving a note for his wife. He returned to Canada long enough for his wife to die of a mysterious illness, a death for which he would later be blamed. He went to Edinburgh to practice medicine, but when a woman with whom he was alleged to have had an affair was found dead, pregnant and poisoned by chloroform in an alleyway in August 1879, Cream fled to the United States.
On July 14, 1881, Daniel Stott died of strychnine poisoning at his home in Boone County, Illinois. Cream was arrested, along with Mrs. Julia A. (Abbey) Stott, who had obtained poison from Cream to do away with her husband. Stott turned state's evidence to avoid jail, which left Cream to face a murder conviction on his own. He was sentenced to life imprisonment in Joliet Prison. One night unknown persons erected a tombstone at Mr. Stott's grave which read,
Daniel Stott Died June 12, 1881 Aged 61 Years POISONED BY HIS WIFE & DR. CREAM
Cream was released 10 years later after his brother pleaded for leniency, allegedly also bribing the authorities.
On October 13 that year, Ellen "Nellie" Donworth, a 19-year-old prostitute, went out for a few drinks with Cream. She was severely ill the next day and died on October 16 from strychnine poisoning.
On October 20, Cream went on a "date" with a 27-year-old prostitute named Matilda Clover. She became ill and died the next morning; her death was at first linked to her alcoholism.
On April 2, 1892, after a vacation in Canada, Cream was back in London where he attempted to poison Lou Harvey (nee Louise Harris) who, being suspicious of him, pretended to swallow the pills he had given her. She secretly disposed of them by throwing them off a bridge into the Thames.
On April 11, Cream met two prostitutes, Alice Marsh, 21, and Emma Shrivell, 18, and talked his way into their flat where he offered them bottles of Guinness. Cream left before the strychnine he had added to the drinks took effect. Both women died in agony.
Only three of these are known, but there may have been others who were approached to. First was Frederick Smith the son of the former First Lord of the Treasury and member of the House of Commons William Henry Smith. Fred Smith had just been elected to the seat in the House of Commons his father had held for decades, and he received a letter accusing him of poisoning Ellen Donworth. There was a demand for the hiring of an "attorney" in order to prevent Smith being ruined by release of the evidence. Smith sent the letter to Scotland Yard. Next Mabel, Countess Russell, in the middle of a messy series of civil actions against the Earl Russell that would culminate in a controvertial divorce in 1900, received a letter that her estranged husband was responsible for the poisoning and evidence of this could be purchased. This was a variant on the normal blackmail notes, for if it had been true the Countess would have been overjoyed to have had such information in her hands. She claimed she showed the letter to her solicitor Sir George Henry Lewis but after he returned it she lost it. There may be a chance she actually met Cream and had to return the letter to him, but that nothing came of his "evidence" against the Earl. Finally Cream wrote a note to the noted physician Dr. (later Sir) William Broadbent. The note accused Broadbent of poisoning Matilda Clover. Broadbent sent his letter to Scotland Yard.
Cream's downfall came through an attempt to frame two respectable and innocent doctors. He wrote to the police accusing these fellow doctors of killing several women, including Matilda Clover. Not only did the police quickly determine the innocence of those accused, but they also realized that there was something significant within the accusations made by the anonymous letter-writer: He had referred to the murder of Matilda Clover. In fact, Clover's death had been noted as natural causes, related to her drinking. The police knew that the false accuser who had written the letter was the serial killer now referred to in the newspapers as the Lambeth Poisoner.
Not long afterwards, Cream met a policeman from New York City who was visiting London. The policeman had heard of the Lambeth Poisoner, and Cream gave him a brief tour of where the various victims had lived. The American lawman happened to mention it to a British policeman who found Cream's knowledge of the case suspicious.
The police at Scotland Yard put Cream under surveillance, soon discovering his habit of visiting prostitutes. They also contacted police in the United States and learned of their suspect's conviction for a murder by poison in 1881.
On July 13, 1892, Cream was charged with murdering Matilda Clover. From the start he insisted he was only Dr. Thomas Neill, not Dr. Thomas Neill Cream, and the newspapers usually referred to him as Dr. Neill in their coverage of the proceedings. His trial lasted from 17 to 21 October that year. He was convicted and sentenced to death.
Less than a month after his conviction, on November 15, Dr Thomas Neill Cream was hanged at Newgate Prison.
It may be pointed out that the rumor that Cream said this was started by his executioner, James Billington. Billington was a known practical joker, and it is very likely that he knew that the listeners would think that it was a shame Cream did not have a chance to tell the full story of his confession before he hanged. But if one analyzes it, it is a kind of joke - a man about to hang for four poisonings is prevented from confessing to five mutilation murders, which (had he done them and been captured) would have resulted in his...being hanged!
The criminal historian, Jonathan Goodman, had a suggestion in his book (with Bill Waddell (Curator)), The Black Museum: Scotland Yard's Chamber of Crime (London: Harrap, Ltd, 1987), that Cream, in his last moments on the scaffold, was so frightened he could not control his body functions, and said, "I am ejaculating."