<p>Studies have shown that decorin is a potent pan-cancer tumor suppressor that is under-expressed in most cancers. Decorin interacts with receptor tyrosine kinases and functions as a pan-receptor tyrosine kinase inhibitor, thereby suppressing oncogenic signals. Decorin deficiency promotes epithelial-to-mesenchymal transition and enhances cancer dissemination and metastasis. According to recent GLOBOCAN estimates, the most common cancers worldwide are breast, lung, prostate, colorectal, skin (non-melanoma), and stomach. Considering the burden of rising cancer incidence and the importance of discovering novel molecular markers and potential therapeutic agents for cancer management, we have outlined the possible expressional and clinicopathological significance of decorin in major cancers based on available pre-clinical and clinical studies. Measuring plasma decorin is a minimally invasive technique, and human studies have shown that it is useful in predicting clinical outcomes in cancer though it needs further validation. Oncolytic virus-mediated decorin gene transfer has shown significant anti-tumorigenic effects in pre-clinical studies, though its implication in human subjects is yet to be understood. Exogenous decorin delivery in experimental studies has been shown to mitigate cancer growth, but its therapeutic efficacy and safety are poorly understood. Future research is required to translate the tumor-suppressive action of decorin observed in preclinical experiments to therapeutic interventions in human subjects.</p>