Tumour lysis syndrome (TLS) is a medical emergency occurring when large numbers of cancer cells rapidly undergo cell death. The resultant metabolic abnormalities results in significant morbidity and mortality. Tumour lysis syndrome most commonly occurs in 5% of haematological malignancies and is less commonly described in solid organ cancers. In breast cancer, TLS has been reported to occur both spontaneously and as a result of cancer chemotherapy, targeted therapy, or radiotherapy. However, only 1 TLS case in a breast cancer patient has been reported as a consequence of aromatase inhibitor letrozole. With the increased recent use of CDK4/6 inhibitors, 2 cases of hyperuricaemia in patients with breast cancer treated with palbociclib/letrozole combination treatment have also been reported. We present the second case of letrozole-induced TLS in a 74-year-old woman with occult breast adenocarcinoma. Despite treatment with recombinant urate oxidase and intravenous fluids, the patient deteriorated and was discharged with hospice care. Although rare, this life-threatening condition should be considered in an acutely unwell patient commencing treatment for solid malignant tumours.