Radioactive iodine (RAI) treatment is an effective method for the treatment of thyroid remnant ablation and metastasis in patients with differentiated thyroid cancer. The current guidelines recommend patients to drink lots of water to reduce the amount of iodine in the body during RAI treatment; however, water intoxication is a life-threatening condition resulting from hyponatremia. This case report describes water intoxication during RAI treatment in a 55-year-old patient who was evaluated for the management of angio-invasive follicular thyroid cancer following a total thyroidectomy. Hyponatremia is an electrolyte imbalance commonly encountered in oncology practice and is usually defined as a serum sodium level of less than 135 mEq/L. Water intoxication is a rare phenomenon that occurs due to an excessive intake of water, especially when the volume of water intake exceeds the excretory capacity of the kidney. This case report has revealed that all relevant information and instructions including the consumption of water should be clearly and accurately communicated to patients.