We report a case of relapsed large B-cell non-Hodgkin lymphoma (NHL) affecting the anterior pituitary. The NHL relapsed after three years in complete remission. The patient was a 72-year-old woman who presented fever, weakness, hyponatremia, and hypotension. The levels of thyroid-stimulating hormone and gonadotropins were very low and magnetic resonance imaging showed infiltration of the pituitary gland and stalk. After controlling the hormonal deficiencies with substitution using hydroxycortisone and levothyroxin, the patient was treated with combination chemotherapy using cyclophosphamide, vincristine, mitoxantrone, etoposide, and bleomycin (VNCOP-B regimen), achieving a complete regression of the pituitary mass and partial recovery of the endocrine function. Lymphoproliferative disorders affecting the anterior pituitary are exceedingly rare, with only six cases in immunocompetent adults reported in the literature. To our knowledge this is the first report of a relapsed NHL presenting by hypopituitarism.