Tumour lysis syndrome (TLS) is a life-threatening complication wherein massive tumour cell lysis results in severe metabolic abnormalities. TLS generally follows chemotherapy of rapidly proliferating haematological malignancies; spontaneous TLS and TLS from treatment of solid tumours are infrequently reported. We present a rare case of TLS following treatment of a large gastrointestinal stromal tumour (GIST) in a 63- year-old man. Imatinib was started for tumour size reduction prior to surgical intervention and in 5 days the patient developed metabolic derangements consistent with TLS. Imatinib was held and fluids, allopurinol and rasburicase were started. All metabolic abnormalities resolved in 3 days. Imatinib was restarted, and he eventually underwent surgical intervention. This is the second case demonstrating successful reinitiation of imatinib following TLS when treating GIST. We highlight the importance of risk factor assessment and need for pre-emptive therapy to prevent TLS when using tyrosine kinase inhibitor therapy.