Thieves forced entry to the Kirkwood Hospice shop in Northgate Centre overnight between Wednesday December 20 and Thursday December 21, and made off with a safe, cash and a laptop computer.
Police want to speak to anyone who might have come across the "large free-standing safe."
PC Cara Papworth of Kirklees District Police, said: “Any theft from a charity benefiting others is an abhorrent act and we are appealing for information from anyone who can help us identify those responsible.
“I am particularly keen to speak with anyone who may have seen a large free standing safe abandoned in the local area or who may have knowledge of its whereabouts.”
She added: “We do know the shop was broken into overnight, most likely at about 3.30am on the Thursday, and we would also like to speak with anyone who may have seen suspicious behaviour at that time or who may have CCTV which captures the offenders nearby.
Call police on 101 or ring Crimestoppers anonymously on 0800 555 111.