Lung cancer is the leading cause of cancer death in the world. Despite developments in personalized treatment, lung cancer is still problematic for therapy due to resistance and metastasis. Moreover, heterogeneity of lung cancers makes treatment difficult. Therefore, there is an urgent need to find novel prognostic and diagnostic markers. Desmosomal proteins seem to be a good candidate to be acknowledged due to their function in the cell. Desmosomal proteins are known to be responsible for accurate cell–to–cell adhesion in physiological conditions. In cancer cells, the destabilization of desmosomes by the loss of proteins promotes the process of epithelial-mesenchymal transition, which is strongly connected to metastasis. Desmoglein 3 is one of the desmosomal proteins often deregulated in cancer, including lung cancer. Taking the above, our goal was to analyze the results on DSG3 function and its clinical implications in lung cancer.