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RealAge answeredUpper mouth pain can be caused by a number of medical issues from a toothache or sore throat to more serious illnesses such as cancer. Certain diseases and their treatments may also be an underlying cause of upper mouth pain. For example, people with human immunodeficiency virus (HIV) may find it painful to eat or swallow, and those who receive cancer treatment may develop mouth sores. It is best to check with your dentist or doctor about any prolonged pain in your mouth, because it could be related to other illnesses in your body.Helpful? 2 people found this helpful.