Background <p>Sinusoidal obstruction syndrome (SOS) is a type of drug-induced liver injury already reported in several oncological settings including metastatic colorectal cancer, hematopoietic stem cell transplantation, and advanced gastric cancer. This study aims to investigate the spectrum of pathological alterations occurring to the liver in breast cancer patients under medical treatment.</p> Methods <p>All patients undergoing liver resection for metastatic disease at Humanitas Cancer Center (&gt; 1000) cases were retrieved. Among them, 15 patients had a breast cancer metastasis, after medical therapy, and available non-neoplastic tissue. This latter was stained with H/E, Masson’s trichrome, CD34, Glutamine Synthetase and SMA. Morphology- and immunohistochemical- score were used to investigate possible association with medical regimen.</p> Results <p>Sinusoidal dilatation and centri-lobular fibrosis were seen in 100% and 93%. Perisinusoidal fibrosis, perisinusoidal hemorrhage and peliosis in 40%, 13% and 47%; nodular regenerative hyperplasia (NRH) was seen in 7% (one patient). Severe SOS was associated with more aggressive therapeutic regimen, such as the use of chemotherapy as last treatment before surgery (p: 0.013) or ≥ 4 treatments (p: 0.065). The most severe case presented in a patient treated with Trastuzumab Emtansine (T-DM1).</p> Conclusions <p>This clinic-pathological study proved that patients receiving aggressive medical treatments for breast cancer are likely to develop a SOS. The spectrum of this disease, rather than in the surgical specimen (used herein as a matter of proof), may be insidious in liver biopsy performed for staging purpose.</p>