NEW YORK — Spencer Johnson, who left behind a medical career to write short books about life and business, including “Who Moved My Cheese?’’ — a parable about embracing change that has sold 28 million copies worldwide — died Monday in San Diego. He was 78.

The cause was complications of pancreatic cancer, said Nancy Casey, his executive assistant.

“Who Moved My Cheese?,’’ which was published in 1998, was the story — in 94 pages of large type — of two mice, Sniff and Scurry, and two tiny people, Hem and Haw, looking for cheese in a maze. When the cheese supply runs out at Cheese Station C, the mice leave without angst to find more.

But Hem and Haw resist, refusing to accept change. Haw overcomes his anxiety and ventures out of his comfort zone — at first timidly, but then, gradually, with more confidence — in search of cheese.

“Before long, he knew why he felt good,’’ Mr. Johnson wrote about Haw. “He stopped to write again on the wall: ‘When you stop being afraid, you feel good!’ ’’

The book became a publishing phenomenon and a workplace manual that preached how flexibility in the face of changing times will reward people. Those who are wedded to the past and lag behind, like the intransigent Hem, will not survive.

“Spencer built a fable that helps people deal with change in a really accessible way,’’ said Ivan Held, president of G.P. Putnam’s Sons, which published the book. In an interview, he confirmed its sales figures and said it had been translated into 44 languages.

“Who Moved My Cheese?’’ was not Mr. Johnson’s first blockbuster book. He and Ken Blanchard, a business consultant, collaborated on “The One Minute Manager’’ (1982). The story of a young man searching for an effective manager to work for (and emulate), the book lays out the goals, secrets, praisings, and reprimands that defined effective management.

Mr. Johnson met Blanchard at a party in late 1980. At the time, Mr. Johnson was writing children’s books with his first wife, Ann Donegan, about historical figures such as Winston Churchill, Jackie Robinson, Christopher Columbus, and Confucius.

“He wrote children’s stories, and I made a point of telling stories while doing leadership training,’’ Blanchard said in a telephone interview Thursday. “I was already telling a story about a manager who wouldn’t make decisions, and talking about goals. So we decided to do a story about a man looking for an effective manager.’’

They self-published the book — also a slim volume, at just over 100 pages — to great success before they negotiated a deal with William Morrow & Co. Mr. Johnson’s agent, Margret McBride, said Larry Hughes, then president of Morrow, balked at Mr. Johnson’s plan to charge $15 for the book. Instead, he said, his sales manager wanted to set the price at no more than $7.99.

Mr. Johnson objected, saying that he and Blanchard were already charging $15 and could not meet the demand; before that, they were charging $10 for photocopies of the book.

“If your sales manager feels Morrow can’t do better than we are,’’ Mr. Johnson said, according to McBride, “with all the infrastructure we have available, we might as well part ways now.’’

Hughes agreed. Morrow charged $15 a copy with a money-back guarantee and a gold stamp on its cover that exclaimed, “Small, Expensive and Invaluable!’’ It, too, has sold millions of copies.

Patrick Spencer Johnson was born on Nov. 24, 1938, in Watertown, S.D. His father, Jerauld Johnson, was a builder, and his mother, the former Madeline Sankey, was a teacher. He grew up in Los Angeles, earned a bachelor’s degree in psychology at the University of Southern California, then graduated from the Royal College of Surgeons in Ireland.

With medical clerkships at the Mayo Clinic and Harvard Medical School, he seemed assured of a physician’s career. But while working in a hospital, he grew frustrated at seeing the same patients return with the same ailments, as if they were not trying to better their lives, McBride said in an interview.

“He felt a lot of diseases were people lacking something in their soul,’’ she said. “He wanted to fix them from the inside.’’

He went on to work in Minnesota for Medtronic, a medical device manufacturer, as its director of communications. Using his medical background and a simple writing style, he wrote short books to help customers understand complicated technical information.

A best-selling author for more than 30 years, Mr. Johnson assiduously avoided publicity. He refused to have his photograph on his book jackets and rarely did interviews.

“He was not very interested in the spotlight,’’ said Adrian Zackheim, the president and publisher of Penguin Portfolio, who edited Mr. Johnson’s book “The Precious Present’’ (1984) for Doubleday. “He was interested in writing his books and having an impact without saying much beyond them.’’

Although his books were short, it took Mr. Johnson years to write them, he told USA Today in 2003. He also solicited input from people around him to improve his manuscripts.

“Most writers write the book they want to write,’’ he said to USA Today. “You’re much wiser if you write the book people want to read.’’