"I was a surgeon, but I found myself not good at surgery," said the Japanese professor, describing why he changed his career from medicine to stem cell research.
Yamanaka has been incredibly successful in his second career and was this week awarded a share of the Shaw Prize, a million-dollar science award set up by Hong Kong philanthropist and film mogul Run Run Shaw.
The award recognised Yamanaka's moment of genius, when he discovered how to turn skin cells into stem cells, the so-called master cells which can develop into any of hundreds of different cell types in the body, replacing those lost or damaged by disease.
Stem cell therapy has been touted as a promising intervention for neurodegenerative diseases such as Parkinson's or Alzheimer's, as well as helping create new drugs and improving research.
Although his technique is a long way from being perfected, it has created a potential alternative to stem cells harvested from embryos, a procedure that has provoked the ire of pro-life and religious groups across the world.
The new technique is so promising that one of the men who created the world's first cloned sheep, Dolly, and who shared the Shaw Prize with Yamanaka, has stopped cloning embryos to focus on studying stem cells derived from skin cells.
While Yamanaka is not against embryonic stem cell research -- he said he would use his wife's embryos if he needed to -- he does hope he has provided a potential, elegant solution.
"I was a physician, so the biggest concern for me was to help patients," said the Kyoto University professor.
"If embryo stem cell research is the only way to help patients, then I think that is what we should do.
"At the same time... as a natural feeling, I do want to avoid the usage of human embryos... Human embryos are not like skin cells, they can be babies if transplanted. That is why we are doing what we are doing."
Yamanaka is acutely aware his new science is creating new ethical dilemmas and is a supporter of firm regulation.
"We should limit the application of technology to treatment or what can make patients happier," he said.
"We may be able to generate new life (with this technique), so we are presenting another ethical issue with this problem."
He draws the line at creating a new life simply to grow new organs, theoretically possible using his technique.
"It is technically very difficult (but) organ shortage is a big problem right now in many countries. We need some kind of regulation," he said.
Born in 1962, Yamanaka was the only son of a factory owner, who produced parts for sewing machines.
When he was in his early teens, his father told him that he should not follow the traditional Japanese path and take over the business, but become a doctor.
"He said it was more useful," said the father of two, whose eldest daughter is at medical school.
While Yamanaka followed his father's wish, he found his niche when he turned away from medicine. But his new-found fame -- which has seen his work praised by US President George W. Bush and the Roman Catholic Church -- has created new pressure.
"Yes, it has been very stressful," he said, adding the pressure was why he avoided giving a timetable for the development life-saving treatments that could follow his work.
"It is quite dangerous to predict. If I say five years for some disease, patients suffering from that disease will expect it. After five years they may be very disappointed. I think we should avoid too much hype."