Gastric cancer is one of the most common cancers worldwide and is one of the deadliest types of neoplasm. Many patients present with an advanced stage where palliative chemotherapy is the standard of care. 5-Fluorouracil (5-FU) remains the backbone of systemic therapy treatment in advanced gastric cancer, although is associated with many side effects. While cases of encephalopathy caused by hyperammonemia have been reported, lactic acidosis after systemic 5-FU exposure is exceedingly rare. We present here for the first time a case of type B lactic acidosis secondary to mFOLFOX6 therapy in advanced gastric cancer. This patient presented with acute delirium, dystonia, and a lactate of 11.7 mmol/L, which peaked to 18.7 mmol/L, within 48 h of chemotherapy treatment. Routine clinical monitoring of lactate may be beneficial to avoid this potentially life-threatening adverse event.