Oral dichloroacetate sodium (DCA) is currently under investigation as a single agent and as an adjuvant for treatment of various cancers. One of the factors limiting its clinical use in a continuous oral regimen is a dose-related, reversible neurotoxicity, including peripheral neuropathy and encephalopathy. The intravenous (IV) route has a number of potential advantages, including (1) pulsed dosing to achieve higher concentrations than feasible with oral use, (2) a longer washout period to reduce the potential for neurotoxicity, and (3) a bypassing of the digestive system, which is particularly significant for advanced-stage cancer patients. Data were available on high-dose IV DCA (up to 100 mg/kg/dose) that have confirmed its safety, both in healthy volunteers and in critically ill patients, allowing the authors to begin off-label treatment of cancer patients. In several of their patients treated with IV DCA, the authors observed clinical, hematological, or radiological responses. This article presents 3 cases with patients who had recurrent cancers and for whom all conventional therapies had failed: (1) a 79-y-old male patient with colon cancer who had liver metastases, (2) a 43-y-old male patient with angiosarcoma who had pancreatic and bone metastases, and (3) a 10-y-old male patient with pancreatic neuroendocrine carcinoma who had liver metastases.