PURPOSE: Renal angiomyolipoma in patients with tuberous sclerosis can cause life-threatening bleeding. Embolization or resection is recommended, but either intervention may result in substantial loss of renal function. Recently, regression of angiomyolipoma size has also been achieved with mTOR inhibitor therapy, but recurrent lesion growth after treatment cessation has to be expected. This is the first report on a multimodal therapeutic approach facilitating a nephron-sparing, definitive resection. METHODS: Three patients with renal angiomyolipoma not amenable to nephron-sparing surgery were treated with sirolimus aiming trough levels of 4-8 ng/ml. Treatment was well tolerated. RESULTS: mTOR inhibitor treatment resulted in a regression of angiomyolipoma volume by 38-95 %. Thereafter, nephron-sparing angiomyolipoma resection conserved normal renal function. CONCLUSION: Neoadjuvant use of mTOR inhibitor pretreatment may represent a novel approach facilitating nephron-sparing resection.