S100A10, a member of the S100 protein family, commonly forms a heterotetrameric complex with Annexin A2. This is essential for the generation of cellular plasmin from plasminogen, which leads to a cascade of molecular events crucial for tumor progression. S100A10 upregulation has been reported in a number of cancers, suggesting that it may have potential as a prognostic biomarker, as well as predicting sensitivity to anticancer drugs. This review evaluates the direct and indirect relationships between S100A10 and cancer progression by investigating its role in cancer. Research papers published on PubMed and Google Scholar between 2007–2017 were collated and reviewed. We concluded that S100A10 affects the development of the hallmarks of cancer as explained by Hanahan and Weinberg in 2011, most notably by activating the invasion and metastasis of cancer cells. However, further studies are required to explore the underlying biological mechanisms of S100A10.