Gastroesophageal Reflux Disease (GERD) or Peptic Ulcer Disease: These conditions are common causes of epigastric tenderness due to the inflammation of the stomach lining or the duodenum, often related to acid production.

Gastritis: Inflammation of the stomach lining can cause epigastric pain and tenderness, often related to infection, alcohol use, or NSAIDs.
Pancreatitis: Inflammation of the pancreas, which can be acute or chronic, often presents with epigastric pain radiating to the back.
Cholecystitis: Inflammation of the gallbladder, usually due to gallstones, can cause epigastric pain, especially after eating fatty foods.

Myocardial Infarction: Although chest pain is the typical presentation, some patients, especially women and diabetics, may present with epigastric discomfort or nausea, making it crucial not to miss this potentially fatal condition.
Pulmonary Embolism: While more commonly presenting with respiratory symptoms, a pulmonary embolism can occasionally cause epigastric pain if the embolism affects the lung's lower lobes.
Aortic Dissection: A tear in the aorta's inner layer can cause severe, tearing pain that may be referred to the epigastric area, especially if the dissection involves the descending aorta.

Splenic Infarction: Although the spleen is located in the left upper quadrant, a large splenic infarct can cause referred pain to the epigastric area.
Hepatic Abscess or Infarction: Liver conditions can occasionally present with epigastric pain, especially if the process involves the left lobe of the liver.
Diabetic Ketoacidosis: This serious complication of diabetes can cause abdominal pain, including in the epigastric area, due to metabolic disturbances.