Background: PEComa is a rare mesenchymal neoplasm composed of perivascular epithelioid cells. Due to its rarity, diagnosis is challenging and no standardized treatment guidelines have been established. A subgroup of PEComas are characterized by a loss of function mutation in TSC1/2 that activates the PIK3-Akt-mTOR pathway. In the majority of patients, however, the molecular landscape and the composition of the tumor microenvironment (TME) remain largely unclear. Thus, we conducted this study to elucidate the genetic landscape of PEComas. A comparative analysis was performed with melanoma as a representative immunogenic tumor type.