Simple SummaryRecurrence in soft-tissue sarcomas represents a major drawback in the therapeutic management of patients. It may lead to amputation in cases of extreme STS or even to a therapeutical cul-de-sac in other localizations. The molecular identification of patients that are likely to develop a recurrence would represent a major breakthrough in adapting treatment and monitoring patients at risk. In this project, we identified two distinct cellular profiles of peritumoral tissue associated with different clinical behavior. This characterization could help clinicians to tailor neoadjuvant treatments based on a given patient’s risk.AbstractBackground: The management of soft-tissue sarcoma (STS) relies on a multidisciplinary approach involving specialized oncological surgery combined with other adjuvant therapies to achieve optimal local disease control. Purpose and Results: Genomic and transcriptomic pseudocapsules of 20 prospective sarcomas were analyzed and revealed to be correlated with a higher risk of recurrence after surgery. Conclusions: A peritumoral environment that has been remodeled and infiltrated by M2 macrophages, and is less expressive of healthy tissue, would pose a significant risk of relapse and require more aggressive treatment strategies.