The piece was discovered at Compton Care's flagship store in St George's Parade, Wolverhampton, when staff arrived at work earlier this week.
It comes after a mystery was sparked last month when a Banksy-esque design was spotted in Waterloo Road, which belonged to graffiti artist Skore.
The latest artwork depicts a smartly-dressed man in a bowler hat who appears to be stoking a fire on the side of the building, formerly home to Wilko.
Senior store manager Mike Evans, who made the discovery on Monday morning, said: "It’s not the sort of thing you expect to see when you come into work, but it’s certainly got us all talking and wondering whether it could actually be the real thing.
"Although it would have even better if the mysterious artist had popped in afterwards to find a few bargains or have a bite to eat in our on-site coffee shop."
It comes after the building in St George's Parade was flooded in October – after thieves stole parts from the water piping system – which flooded the shop floor and caused the palliative care charity, based in the city, to lose around £10,000 after it was forced to temporarily close its doors.
The superstore is open Monday to Saturday from 8am-5.30pm, with all purchases made helping to fund Compton Care’s work to help families living with the effects of incurable and life-limiting conditions.