Background and Objective: Soft tissue sarcomas (STS) are rare malignancies. Their low incidence and the complexity of their management demand their treatment at high-volume multidisciplinary centers to ensure an adequate quality of care. This study aimed to assess the epidemiology, quality of care, and costs of care for cases of STS in the Veneto Region. Methods: This retrospective, population-based study included all incidental cases of STS recorded in the Veneto Region (northeast Italy) in 2017 and 2018. The 1990-2018 temporal trends in the age-standardized incidence of STS were also obtained by sex. Then significant changes in yearly rates for males and females were identified using a joinpoint regression. The quality of care in different phases of the STS clinical pathway was assessed by computing the real-practice values of a set of indicators established by a regional multidisciplinary working group. The average survival-weighted, real-world costs per patient at 2 years after their diagnosis were extracted from regional administrative databases and stratified by sex and TNM stage. Results: The incidence of soft tissue sarcoma was generally higher in males than in females. The temporal trends were flat for women, and rose slightly trend for men (APC = 0.9, p-value = 0.001). The survival-weighted mean total cost per patient amounted to €22,183 (€40,042 for stage IV disease and €10,379 for stage I). Adherence to diagnostic procedures, such as the proportion of initial anatomopathological diagnoses supported by a second opinion, was poor. Indicators concerning the surgical treatment of intermediate/high-grade and retroperitoneal STS were still significantly lower than the thresholds as only 37% of the latter were treated with multivisceral surgery. Conclusions: The availability of a high-resolution registry enabled a population-based epidemiological investigations on the direct costs of illness for patients with STS, affording an overview of the quality of their clinical care pathways.