In TLS, the breakdown occurs after cytotoxic therapy or from cancers with high cell turnover and tumor proliferation rates.

These factors include elevated baseline serum creatinine, kidney failure, dehydration, and other issues affecting urinary flow or the acidity of urine.

[7] Usually, the precipitating medication regimen includes combination chemotherapy, but TLS can be triggered in cancer patients by steroid treatment alone, and sometimes without any treatment—in this case the condition is referred to as "spontaneous tumor lysis syndrome".

[13] TLS should be suspected in people with large tumor burden who develop acute kidney failure along with hyperuricemia (> 15 mg/dL) or hyperphosphatemia (> 8 mg/dL).

[16][17] It is not recommended to alkalinize urine in the management of TLS: although doing so increases the solubility of urste, it also creates calcium phosphate crystals.

[2][4] Insulin therapy (in conjunction with glucose administration) as well as beta-receptor agonists (such as albuterol) can also be used, but are temporary interventions,[2] and potassium is not excreted from the body.

In general, rasburicase and hydration are the mainstays of treatment in patients with clinical evidence of tumor lysis syndrome.

[18] Further treatment is targeted towards the specific metabolic abnormalities present in patients with TLS (see "main articles" linked above).

Mild hyperkalemia without symptoms can be treated with a loop diuretic and sodium polystyrene sulfonate, while a temporizing agent such as rapid acting insulin (in conjunction with glucose) and an agent to stabilize cardiac membranes such as calcium carbonate may be given in cases of severe hyperkalemia.

[18] The rate of mortality from tumor lysis syndrome may vary widely depending on the type of underlying malignancy.