The process allows single letter mutations not only to be introduced to cells but accurately identified.
Using the technique, researchers were able to spot one mutant in a sample of 1,000 cells.
The research raises the prospect of accurately modelling human diseases in the laboratory, as well as finding cures that fix specific disease mutations.
"Our method provides a novel way to capture and amplify specific mutations that are normally exceedingly rare," said lead scientist Dr Bruce Conklin, from the Gladstone Institutes in California, US.
The human genetic code, written in DNA, is made up of repeating sequences of four chemical "building blocks" designated by the letters A, C, T and G.
Substituting just one letter for another can lead to devastating diseases.
Examples are sickle cell anaemia, haemophilia, the "accelerated ageing" disease progeria, and proteus syndrome - the tissue overgrowth condition believed to have afflicted Joseph Merrick, the "Elephant Man".
Cystic fibrosis, which destroys the lungs, is caused by the deletion of three code letters.
A major challenge for scientists is the fact that such mutations can be very rare, often affecting as few as 1% of cells.
"For our method to work, we needed to find a way to efficiently identify a single mutation among hundreds of normal, healthy cells," said Gladstone co-author Dr Yuichiro Miyaoka.
"So we designed a special fluorescent probe that would distinguish the mutated sequence from the original sequences. We were then able to sort through both sets of sequences and detect mutant cells - even when they made up as little one in every 1,000 cells.
"This is a level of sensitivity more than one hundred times greater than traditional methods."
The scientists used artificially made stem cells called induced pluripotent stem (iPS) cells as a tool in their research.
An advanced technique called TALENs, which employs an enzyme as a genetic cutting device, was first used to introduce specific mutations into the iPS cells.
The fluorescent probe then made it possible to pinpoint where the DNA changes were.
"Our high-efficiency, high-fidelity method could very well be the basis for the next phase of human genetics research," said Dr Conklin.
"Some of the most devastating diseases we face are caused by the tiniest of genetic changes. But we are hopeful that our technique, by treating the human genome like lines of computer code, could one day be used to reverse these harmful mutations, and essentially repair the damaged code."
The research is published in the journal Nature Methods.