Malignant PEComa is extremely rare and is frequently associated with germline or somatic loss-of-function mutations in the tuberous sclerosis 1 (TSC1) or tuberous sclerosis 2 (TSC2) genes, which leads to activation of the mTOR pathway, suggesting sensitivity to mTOR inhibitors. Here, TSC1 is linked to neoplasm with perivascular epithelioid cell differentiation.