Tumour lysis syndrome (TLS) is a rare but serious complication of cancer treatment. It is generally seen in patients with high tumour load or chemosensitive tumour after chemotherapy and is more common with haematological malignancies like leukaemia and lymphoma when compared to solid tumours. TLS occurring after radiotherapy (RT) in patients with solid tumours is very rare. We aimed to present TLS seen after RT for a vertebral tumoral mass in a patient with metastatic adenocarcinoma of unknown origin. A 78-year-old woman, who was diagnosed with adenocarcinoma of unknown origin, was hospitalized to undergo palliative RT for the vertebral mass. On the 1st day, 4 mg q6hour perioral dexamethasone was started. 300 cGy per session RT started on the 2nd day of hospitalization. After the fifth session of RT (after a total dose of 15 Gy), she developed TLS complicated with acute kidney injury requiring renal replacement therapy and she was successfully treated by haemodialysis. Close monitoring, even in patients with low risk for TLS and early administration of preventive modalities should be kept in mind.