Chest pain with esophageal origin is a symptom whose prevalence is over 10 % in our setting. Esophageal and cardiac innervation have common nociceptive pathways and characteristics that require a differential diagnosis for cardiac causes, fundamentally of the ischemic heart disease, in many of the cases. Among the digestive causes, the most frequent are gastroesophageal reflux, esophageal motor disorders and esophageal hyperalgesia. However, a differential diagnosis should be made of other conditions, such as musculoskeletal disorders and pulmonary diseases. The clinical history followed by physical examination will orient the diagnostic decision making, it being possible to choose a treatment test period with high proton pump inhibitors for 1-4 weeks in the mild cases. This will help to discriminate some cases of gastroesophageal reflux disease (GERD) and will avoid the following complementary tests that include oral panendoscopy, 24-48 hour esophageal pHmetry and/or impedance pHmetry, stimulation tests combined with the esophageal manometry that will lead to the final diagnosis in most of the cases.