Eosinophilic esophagitis (EoE) has been recognized as a chronic disease of the esophagus with significant involvement of the mucosal immune system. Similar conditions in other gastrointestinal diseases have led to a malignant transformation (ie, inflammatory bowel disease, celiac disease, etc). MIB-1 (Ki-67) and p53 are monoclonal antibodies that are used to detect early markers for dysplastic changes, possibly leading to cancer development in adult patients with chronic gastroesophageal reflux disease (GERD), Barrett's esophagus, and/or the adenocarcinoma sequence of the esophagus. Only limited studies of these cell markers have been published in children with EoE. The aim of this study is to examine p53 and Ki-67 cell markers in children with EoE before and after medical therapy. The immunohistochemical staining of cell markers p53 and Ki-67 was examined in esophageal biopsies of children diagnosed with EoE, GERD, and normal esophagus. In addition, biopsies from adults with EoE and adenocarcinoma were used as positive controls. In 10 children who were successfully treated for EoE, immunohistochemical staining was compared before and after medical therapy. The immunohistochemical staining of p53 and Ki-67 was increased in children with EoE compared with children with a normal esophagus but not in children with GERD. Children with EoE posttherapy had significantly lower immunohistochemical staining for both markers compared to pretreatment staining. p53 and Ki-67 markers are associated with cell proliferation in children with EoE but do not represent a premalignant (dysplastic) condition of the esophagus.