An 8-year-old, spayed female, domestic shorthair cat with a history of hyperthyroidism, anorexia, dehydration, cervical ventroflexion, and behavioral changes was referred to the Iowa State University College of Veterinary Medicine. The cat was obtunded, with severe dehydration (15%) and hypothermia (86 degrees F), and severe muscle atrophy and fasciculations. Serum biochemical abnormalities included severe hypernatremia (195 mmol/L, reference interval 155-165 mmol/L), hyperchloridemia (161 mmol/L, reference interval 123-131 mmol/L), and hypokalemia (3.6 mmol/L, reference interval 4.0-5.7 mmol/L). Calculated osmolality was 418 mOsm/kg (reference interval 280-305 mOsm/kg), attributable to the hypernatremia. The cat was kept warm and given fluid and glucocorticoid therapy and supportive measures but remained unresponsive. Hypernatremia and hyperosmolality improved through day 3, when the cat died suddenly. At necropsy, a 1.25-cm mass was found in the area of the thalamus and interthalamic adhesion that extended to the ventral aspect of the cerebrum. The histologic and immunohistochemical diagnosis was B-cell lymphoma. Hypernatremia and hyperosmolality in this cat were attributed to primary adipsia and hypothalamic dysfunction secondary to effacement of central nervous system tissue by neoplastic lymphocytes. To the authors' knowledge, this is the first reported case of central nervous system lymphoma, confirmed by use of immunohistochemical analysis as a B-cell phenotype, associated with hypernatremia. It also is the first reported case of lymphoma in animals limited to the thalamus, hypothalamus, and cerebrum, with no involvement of the spinal cord.