Dewayne Johnson, a 46-year-old father of two, says he is sick because of contact with Roundup, the top-selling weed killer made by the US company.
The decision by U.S. District Judge Vince Chhabria in San Francisco, California, followed years of litigation and weeks of hearings about the controversial science surrounding the safety of the chemical glyphosate, the key ingredient in Monsanto's top-selling weed-killer.
The first case to be heard is that of a former school groundskeeper, Dewayne Johnson, of whom doctors said is already dying of non-Hodgkin's lymphoma in just a matter of years.
Lawsuits by more than 400 farmers, landscapers and consumers who claim Roundup caused them to develop non-Hodgkin's Lymphoma, a type of blood cell cancer, have been consolidated before Chhabria.
Monsanto has vehemently denied such a connection.
There have been conflicting scientific findings on whether glyphosate caused cancer or not.
Monsanto says in court filings that glyphosate has been deemed safe by "every major regulatory agency". Farmers in California, the most agriculturally productive state in the USA, use it on more than 200 types of crops.
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Chhabria later called the opinions of the plaintiffs' experts "shaky", though he said they still may meet scientific standards to go before a jury.
But serious doubts remain as the World Health Organization in 2015 classified glyphosate as "probably carcinogenic to humans". Homeowners, meanwhile, used Monsanto Roundup on their lawns and gardens.
Monsanto faces 5,000 lawsuits nationwide alleging Roundup caused cancer, mainly in state courts.
Monsanto also pointed to sections of the opinion that questioned the plaintiffs' evidence.
The U.S. Environmental Protection Agency last September concluded glyphosate is likely not carcinogenic to humans.
A federal judge in Sacramento has blocked California from requiring that Roundup carry a label stating that it is known to cause cancer, saying the warning is misleading because nearly all regulators have concluded that there is no evidence glyphosate is carcinogenic.