Background: Breast cancer (BRCA) remains the most common malignancy among women worldwide. Invasive ductal (IDC) and invasive lobular breast cancer (ILC) are the most frequent histological subtypes. Many genetic heterogeneities are related to the carcinogenesis of breast cancer, but exact reasons are still unclear. The study aimed to perform a clinical multivariate analysis of CLDN11 in ILC and IDC. Methods: Datasets analyzed CLDN11 expression in IDC and ILC from The Cancer Genome Atlas (TCGA) database, and the multiple analysis of stratification in terms of clinical pathologic features and CLDN11 was using the Chi-square test. Results: CLDN11 expression was significantly decreased in IDC and ILC data of GEO and TCGA compared to the normal breast tissues. Besides, CLDN11 is negatively correlated with pro-oncogene IKBKE expression and positively correlated with tumor suppressor ETS1 expression in IDC and ILC samples. Multiple factors, including age, clinical stage, subtype, and mutation status, indicated that the expression of CLDN11 is positively associated with the progression of IDC and ILC.Conclusions: CLDN11 acted as a tumor suppressor in IDC and ILC patients and serves as a drug-gable target against IDC and ILC.