This case report illustrates how SIRT can be successfully used in the treatment of a patient initially deemed unsuitable for potentially curative therapy as resection or LT, and how an aggressive and multimodality approach is an important tool in the downstaging strategy. The epicrisis of the clinical case exposed demonstrates a very important concept when applied to this particular variant of HCC, recognized to be more aggressive and with limited access to LT. In the case of the treated patient, the use of an aggressive downstaging treatment schedule reduced the risk of oncological recurrence after transplant, making it comparable to that of HCC within the Milan criteria. The treatment with SIRT has now been included among the curative treatments of both hepatocarcinoma and cholangiocarcinoma; in our case, it has been demonstrated how this effectiveness has allowed not only the inclusion in the transplant list, but to significantly reduce posttransplant tumor recurrence. The oncological aggressiveness of the mixed variant of HCC is also caused by an often late diagnosis. As in the case of our patient, cHCC/CCa most often occurs in non-cirrhotic liver, therefore in patients not under active ultrasound or radiological surveillance. This makes even less feasible the initial transplant consideration and increases the importance of assessing the potential biological response of the neoplasm to locoregional treatments. Mazzafero demostrated in 2020 in the XXL trial that after effective and sustained downstaging of eligible hepatocellular carcinomas beyond the Milan criteria, LT improved tumor-free survival and overall survival compared with non-transplant therapies [13]. The previous guidelines 2018 suggest bridging to LT within the Milan criteria as a neoadjuvant therapy with the aim to limit the drop-out and the recurrences post LT, with low evidence, and with a strong grade of recommendation, particularly if the waiting time on the list is expected to be at least 6 months [2,14]. Progression after endovascular therapies seems to revest a prognostic role, and the treatment response a surrogate biomarker [15]. For the downstaging purpose, Ettorre et al demonstrated good results with SIRT [16]. A world review of 178 patients treated with SIRT mostly in a downstaging strategy shows promising results and a recent work of Salem group reports their experience of 207 transplants after SIRT in bridging and downstaging, with survival similar to non-oncologic transplant [17, 18]. Furthermore, after hepatic surgery, SIRT has proven to be a safe procedure, even after major hepatectomy [19, 20]. Hepatic function evaluation and accurate calculation of the liver absorbed dose with multi-compartimental analysis are mandatory [21]. In our case, we even performed safely the second SIRT at 6-month distance of the first one in the same territory without complications, with a dose to the normal liver of 30 Gy. (Figure 2). In this case, we had a good targeting of the lesions demonstrated by a perfect match between pre-therapy ^99mTc-MAA SPECT/CT and post-therapy SPECT/TC, with tumor absorbed doses of 88, 78 Gy, either predictive factors of good result [22]. We obtained a complete pathologic response at the histologic examination of the explanted liver. This data is important as we know that necrosis at explant is an independent factor of survival after transplant. It utterly confirms that the ablative propriety of SIRT fits the criteria of best treatment modality for bridging [23].