Wales' biggest charity retailer Tenovus has abandoned plans to open 14 shops as the Welsh government considers cutting business rate relief for charities.
And its warning that stores could close was echoed by another charity which said many of its shops could also shut.
The Welsh government has been urged to act by a report which raised concerns that charities were driving other retailers away from high streets.
Ministers are expected to outline their plans on Tuesday.
Proposals include cutting the relief on rates from 80% to 50% for most charity shops and limiting numbers in an area.
Concerns have been raised by some retailers that charity shops, which pay reduced business rates, were taking up retail space and driving traders, who have to pay the charges in full, out of business.
That claim was rejected by those working in the charity sector who say, far from harming other businesses, they are a vital part of the local community.
End Quote Claudia McVie Tnovus chief executive
The money we would lose... would pay for two of our cancer support advisors”
The Charity Retail Association has previously warned that if the proposals went ahead, charities would lose nearly £2m next year, a 15% cut in income
But the proposals have already had an impact according to the chief executive of the cancer charity Tenovus, Claudia McVie.
It has abandoned plans to open 14 shops in the next two years and it warns that it is not only the shops and the staff in them that will be affected, but the charity's wider work.
"The money we would lose... would pay for two of our cancer support advisors," Ms McVie told BBC Sunday Politics Wales.
"Those cancer support advisors see patients day-in and day-out in outreach centres and in communities so the impact is... large for us."
Tenovus added that it would have to decide whether to close some of the shops it has if the Welsh government did introduce the changes.
Meanwhile, the British Heart Foundation has 34 shops in Wales, some of them furniture stores. Another of the proposals being considered by the Welsh government would see the relief abolished for these larger premises.
Delyth Lloyd from British Heart Foundation Cymru said: "We reckon this will severely threaten the viability of our shops in Wales. And we calculate the possible closure of around 10 shops and of course that means a loss of jobs, of over 30 jobs, of managerial staff."
While some small retailers want a more level playing field with charities, the Federation of Small Businesses (FSB) said it had to be kept in context.
Iestyn Davies from the FSB in Wales said: "It's clearly an important subject that does have an impact on our members and does have an impact on the high street.
"However, I don't think you can blame charity shops for every woe that every high street in Wales is having."
He added that vacant premises, out-of-town shopping, planning rules and consumers increasingly buying online were also important factors causing concern to retailers.
The Liberal Democrats and some charities said they had received legal advice that ministers did not have the power to change the rules on relief from business rates unless they first changed the law by introducing a Bill in the assembly.
Many charities argue that if they are driven off the high streets of Wales, they will not be replaced by small retailers but rather by even more payday loans companies, pawnbrokers and empty shops.
The Welsh government has previously said it is "sensitive to the many viewpoints on the issue of business rates relief for charities".
Sunday Politics Wales is on BBC One Wales at 11:00 BST and available on the BBC iPlayer.