Osteopontin (OPN) is an extracellularmatrix protein that is overexpressed in various cancers and promotes oncogenic features including cell proliferation, survival,migration, and angiogenesis, among others. OPN can participate in the regulation of the tumormicroenvironment, affecting both cancer and neighboring cells. Here, we review The role of single-nucleotide polymorphism (SNP)-443 of the OPN gene in cancer aggressiveness.