3D comparisons of Neanderthal, modern human and other primate skulls confirm theories that the ancient people were a breed apart, the researchers report.
Others claim Neanderthals contributed significantly to the modern gene pool.
Details of the research are published in the US journal Proceedings of the National Academy of Sciences.
"If we accept that Neanderthals were not the same species, what we're really saying is they did not contribute at all to modern human populations and in particular modern Europeans," co-author Dr Katerina Harvati of New York University, US, told BBC News Online.
Ancestral contribution
Researchers collected data on 15 standard "landmarks", or features, on over 1,000 primate skulls. Computer software transformed this data into sets of 3D coordinates for each skull and then superimposed all these sets on top of one another.
Using statistical analysis, they compared differences between modern human and Neanderthal skulls with those found between and within 12 primate species.
The results support the view that Neanderthals were indeed a distinct species.
Neanderthals seem to have been a species distinct from our own
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However, other researchers view Neanderthals as a sub-species or population of Homo sapiens that passed on genes to modern humans either by evolving into them or by interbreeding with them.
Evolving hypothesis
The new research shows that differences between Neanderthals and the modern human populations studied are smallest in early Europeans.
Dr Harvati believes this has little significance because the distance is only slightly smaller than that between Neanderthals and living humans.
But John Hawks, assistant professor of anthropology at the University of Wisconsin-Madison, US, disagrees: "It does perhaps suggest that they have some characteristics in common," he said.
THE NEANDERTHALS
The name means 'Man from the Neander Valley'
These human 'cousins' lived 190,000-28,000 years ago
They lived in Europe, Central Asia, and the Middle East
Skulls had large noses and prominent brow ridges
Body shape was stocky and muscular
If interbreeding with Homo sapiens occurred it was limited
"It really is an impressive collection of work," said Dr James Ahern of the University of Wyoming.
But Dr Ahern added that, while the Neanderthal specimens used in the study are all male, several of the early modern Europeans the authors compare them with are female skulls.
"We know that males and females differ greatly in their anatomy, and males will look more archaic than females.
"Because of this, I think the difference they observe between the Neanderthals and the Upper Palaeolithic sample is exaggerated," he explained.
"My own view is that the rate of evolutionary change was great enough that when we compare samples we are going to find that they were different because of the time," said Dr Hawks.
"[Neanderthals] existed at an earlier time and hadn't yet acquired all the characteristics that we have today."
'Lost genes'
This view is at odds with the single origin, or Out of Africa 2, theory, which postulates that all living humans expanded from a single, small population that evolved in Africa more than 150,000 years ago.
As modern humans left their African homeland, they replaced "archaic" humans living in other parts of the world.
Neanderthals appeared in Europe around 190,000 years ago, characterised by a stocky physique ideal for conserving heat in an Ice Age climate.
Shortly after modern humans arrived in Europe 35,000 years ago, Neanderthals disappear from the fossil record.
Studies of mitochondrial DNA from Neanderthal bones also suggest they had little affinity to modern populations.
But some researchers believe this does not exclude the possibility that interbreeding occurred.
Dr Magnus Nordborg, of Lund University in Sweden, has calculated that even if Neanderthals had comprised 25% of the population after merging with modern humans, their DNA might be impossible to detect today.
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