Many head and neck cancer (HNC) patients experience painful therapy-related mucositis and dermatitis. This prospective observational study evaluated transdermal buprenorphine use in HNC patients to relieve treatment-related pain. During treatment with paracetamol or tramadol, visual analogue scale (VAS)-pain scores >30/100 occurred in 26/45 patients 4 weeks after starting cancer therapy, persisting for ≥2 weeks after treatment. These patients subsequently received transdermal buprenorphine. Pain therapy should be more accurately up-titrated to the maximum recommended dose (140 μg/hr) where necessary to maintain pain scores ≤30/100 and, for some patients, should be continued for 6 weeks after the last cancer treatment day.