Cronin was born in Cardross, Dunbartonshire, Scotland, the only child of a Protestant mother, Jessie Cronin (nee Montgomerie), and a Catholic father, Patrick Cronin. Cronin often wrote of young men from similarly mixed backgrounds. His paternal grandparents had emigrated from County Armagh, Ireland, and become glass and china merchants in Alexandria. Owen Cronin, his grandfather, had had his surname changed from Cronague in 1870.

In 1930 Cronin was diagnosed with a chronic duodenal ulcer and was told that he must take six months' complete rest in the country on a milk diet. At Dalchenna Farm by Loch Fyne he was finally able to indulge his lifelong desire to write a novel, having previously "written nothing but prescriptions and scientific papers". From Dalchenna Farm he travelled to Dumbarton to research the background of his first novel, using the files of Dumbarton Library, which still has the letter from Cronin requesting advice. He composed Hatter's Castle in the span of three months, and the manuscript was quickly accepted by Gollancz, the only publishing house to which it had been submitted (it was apparently chosen when his wife randomly stuck a pin into a list of publishers). This novel, which was an immediate and sensational success, launched Cronin's career as a prolific author, and he never returned to practising medicine.  Many of Cronin's books were bestsellers in their day and have been translated into many languages. Some of his stories draw on his medical career, dramatically mixing realism, romance and social criticism. Cronin's works examine moral conflicts between the individual and society, as his idealistic heroes pursue justice for the common man. One of his early novels, The Stars Look Down (1935), chronicles transgressions in a mining community in Northeast England and an ambitious miner's rise to be a Member of Parliament.  A prodigiously fast writer, Cronin liked to average 5,000 words a day, meticulously planning the details of his plots in advance. He was known to be tough in business dealings, although in private life he was a person whose "pawky humour ... peppered his conversations," according to one of his editors, Peter Haining.  Cronin also contributed many stories and essays to various international publications. During the Second World War he worked for the British Ministry of Information, writing articles as well as participating in radio broadcasts to foreign countries.

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