A Vietnamese patient has a form of bird flu virus that has become partially resistant to the antiviral drug experts plan to use to tackle a human outbreak.
The girl may have caught the virus from her brother rather than birds
The UK government has ordered 14.6m doses of Tamiflu, but the Nature report suggests this may not be effective enough if an outbreak does happen.
At present, H5N1 flu strain poses only a limited threat to humans as it cannot spread easily between people.
But experts fear it soon might, and other drugs may be needed to combat it.
However British authorities said the study did not obviate the need to stockpile Tamiflu.
It may be that using Tamiflu (oseltamivir) for too little time or at too low a dose could contribute to the emergence of resistant virus, Yoshihiro Kawaoka from the University of Tokyo and colleagues say.
"Further investigation is necessary to determine the prevalence of oseltamivir-resistant H5N1 viruses among patients treated with this drug," they warn.
The Department of Health said Tamiflu was the internationally agreed product of choice.
"Our antiviral strategy is kept under constant review," added a spokesman.
The 14-year-old Vietnamese girl they describe had been given the drug in February as a preventative measure.
Although she had not had any known direct contact with infected poultry, she had been caring for her 21-year-old brother who was thought to have caught bird flu.
The virus detected in the girl resembled that found in her brother. The girl recovered without any problems, but her case raises the possibility that she could have been infected by her brother, rather than directly by birds.
Also, oseltamivir on its own may not be sufficient to fight a potential H5N1 pandemic and other drugs from the same family such as Relenza (zanamivir) may be needed too, say the researchers.
"Although our findings are based on a virus from only a single patient, they raise the possibility that it might be useful to stockpile zanamivir as well as oseltamivir in the event of an H5N1 influenza pandemic," they said.
Professor Ian Jones, microbiologist at the University of Reading, said: "It's worthwhile noting but it is not unexpected."
He said past studies had shown viruses could become resistant to Tamiflu. He said such resistant strains appeared to be less able to cause harm than the original virus, which was reassuring.
"They don't grow as well so whilst the mutation does arise there is no reason to suppose that [the mutant] virus is going to be a very successful infectious agent."
He added that antiviral drugs did not cure someone of the virus, but merely keep down the levels of infection to allow the body to mount its own response.
"I don't think it obviates the need for stockpiling Tamiflu, but I do agree that it might be useful to have Relenza as well."
A spokeswoman from the Health Protection Agency said: "This is an interesting and important scientific paper and we are aware that resistance is an issue and we have global surveillance.
"But it does not mean that resistant viruses will emerge and transmit effectively."