Claudin-4 (Clostridium perfringens enterotoxin receptor) is a tight junction protein encoded by the gene CLDN4. Expression of Claudin-4 has been associated with either poor prognosis or a more favorable diagnosis, depending on the type of cancer. Claudin-4 has been shown to distinguish adenocarcinoma from malignant mesothelioma with 99% specificity in malignant effusions (1). Claudin-4 overexpression was able to independently predict survival in a breast cancer multivariate analysis as it was associated with poor prognosis, high tumor grade and Her2 expression and was inversely correlated with estrogen receptor staining (2). In luminal breast cancer, the increase of Claudin-4 protein was correlated with the increase of tumor grade and with Ki-67, and thus demonstrated an overall shorter life survival (3). Basal-like tumors also demonstrated overexpression of Claudin-4 (4). Counter to the above breast cancer subtypes, the presence of Claudin-4 in triple negative breast cancer was a biomarker that demonstrated a favorable prognosis (3). Loss of Claudin-4 was also seen in 69% of advanced gastric cancers and correlated with poor differentiation (5). Low expression of the Claudin-4 protein correlated with higher T staging, lymphatic metastasis and higher risk of recurrence in esophageal squamous cell carcinoma (6). Claudin-4 overexpression in prostate cancer may offer a Claudin-4 targeted therapy as a potential treatment (7).