To confirm the diagnosis of eosinophilic esophagitis, an endoscopy is necessary, during which small samples of tissue (biopsies) are taken.
Endoscopy is performed by introducing a thin flexible camera in the oesophagus via the mouth. This allows to inspect the oesophagus and take small biopsy samples. Analysis of these samples under the microscope will show the presence of 15 or more eosinophils per high magnification field. Various endoscopic findings reinforce the diagnosis of eosinophilic esophagitis (esophageal rings, corrugated esophagus, whitish exudates...) but it can also appear normal as well, which is why the simple appearance of the esophagus does not allow the diagnosis to be assured and biopsies are always necessary.

EoE affects only the oesophagus and does not spread to other parts of the body, so the eosinophilic inflammation is not present in the stomach and duodenum. Some diseases such Gastroesophageal Reflux Disease (GERD), may look like EoE and are sometimes difficult to distinguish from EoE.

People with EoE often have other food allergies besides in their esophagus, which do not necessarily cause the EoE. This means that a person may have a food allergy that tests positive on skin or blood tests for IgE, e.g. to nuts, but this allergy is not necessarily the one that causes EoE.