Dozens of calls raising concerns about the underground puppy trade were made in the region last year, new statistics show.
High demands for certain breeds of puppies mean some unscrupulous sellers on online classified websites attempt to plug the gap by offering in-demand breeds and low prices.
But the price is often paid by the owners and animals, with buyers faced with sick and dying puppies that require intensive medical treatment.
Nationally the RSPCA saw its busiest year tackling the underground puppy trade in 2016, receiving more calls than ever from people reporting questionable breeders and dealers.
The charity took 91 calls in Norfolk, 70 in Cambridgeshire and 52 in Suffolk.
The organisation has joined forces with classified website Gumtree to try and crack down on the problem but is also calling for the public's help in tackling the issue.
'Today, particularly with the rise of puppies being advertised and sold online, it's becoming more and more difficult to tell the responsible breeders apart from the unscrupulous ones,' RSPCA dog welfare expert Lisa Richards explained.
'We want all sellers to put the welfare of their dogs and puppies ahead of everything else but, unfortunately, there are many dealers who care only about their profits at the expense of the animals' health and welfare.
'While classified websites, if used responsibly, can be an effective method of advertising for responsible breeders and rescue organisations, sadly far too many people abuse the internet and this has led to many animal welfare issues arising.
'As well as the classified websites, like Gumtree, working with us to crackdown on these dealers, we also need the public's help to stamp out this underground trade.
Morten Heuing, general manager at Gumtree UK, said: 'Whilst most people have safe and successful experiences rehoming dogs on Gumtree, there are a minority of unscrupulous breeders and dealers who put profit ahead of the health and welfare of the animals.
'We take the welfare of animals very seriously and work hard to ensure our site is a safe place to find pets in need of rehoming.'
What to look out for
The RSPCA urges 'anyone thinking of buying a puppy to be extremely careful when they're choosing what type of dog to buy, where to buy from and who to buy from'.
It advises people looking for a dog or puppy do so from a licensed dealer or reputable animal organisation.
RSPCA dog welfare expert Lisa Richards said: 'It's so important to do lots of research not only into the type of dog you want and the kind of care he needs, but also into any potential breeder that you're considering going to.
'We know it's hard but if you're concerned about anything when you visit a breeder, walk away and call the RSPCA and your local authority.'
If you're concerned about a breeder, contact the RSPCA's 24-hour emergency hotline on 0300 1234 999.
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