Targeted anit-cancer drugs in general and Tyrosine Kinas inhibitors specifically have been approved and used recently; so did the understanding of their limitations and side effects. Hitherto, side effects of certain Tyrosine Kinase inhibitors are still being reported with no or little precedents. An example of these rare under reported adverse reactions is hepatic encephalopathy (HE) which has been reported for a total of 11 times with Sunitinib, Regorafenib, Sorafenib and once with Pazopanib. This is a case of a 32-year-old known case of advanced breast adenocarcinoma who underwent neoadjuvant chemotherapy followed by surgery and radiotherapy with excellent response initially but progressed unfortunately to include metastatic chondrosarcoma. Pazopanib has been offered to the patient at her late stages as part of a palliative therapy plan. Soon after, the patient presented to the ER with change in level of consciousness. After ruling out other differentials; HE has been suspected then approved when symptoms resolved after its discontinuation and proper management. The infrequent encounter of HE as a side effect of Pazopanib renders its diagnosis a challenge. This case illustrates the importance of keeping an open mind to rare diagnoses and is a valuable addition to the literature in this matter.