Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a common cause of hyponatremia in cancer patients. It is most frequently reported in association with small-cell lung cancer, but has been reported in other cancers as well. Here we report the case of a patient with myelodysplastic syndrome and blast crisis who developed concurrent hyponatremia. The patient failed to respond to fluid restriction and administration of hypertonic saline. She was treated with tolvaptan, a vasopressin antagonist licensed for the treatment of adult patients with hyponatremia secondary to syndrome of inappropriate antidiuretic hormone secretion. We conclude that in myelodysplastic syndrome patients with blast crisis, inappropriate antidiuretic hormone secretion should be considered as a cause of hyponatremia and be treated with tolvaptan.