In our hypothesis, SARS-CoV-2 and sarcoma coexistence could represent a synergistic interplay, ultimately favoring both viral persistence and tumor proliferation: the overexpression of MDM2 in tumor cells might have generated a favorable immunological niche for SARS-CoV-2 localization and, in turn, SARS-CoV-2 could have favored tumor growth by inducing MDM2-mediated p53 downregulation. This evidence concerns the gene TP53 and sarcoma.