A 77-year-old man presented with adrenocortical insufficiency, for which a cause could not be identified during life. Six weeks after the diagnosis, the patient died, while receiving adequate cortisol therapy, from a fulminant gastrointestinal bleeding. A pleural effusion, found shortly before death, later showed malignant lymphoid cells. At autopsy, a widely spread, diffuse, malignant B-cell lymphoma with destruction of, amongst others, both adrenals was found. The retroperitoneal, but not the peripheral lymph nodes were involved, thereby explaining failure of diagnosis while the patient was living. This is the first description of a diffuse B-cell Non-Hodgkin's lymphoma presenting with adrenocortical insufficiency. Potentially curable malignant invasion of the adrenals can present with adrenocortical insufficiency, and may thus justify imaging of the adrenals with sensitive techniques in elderly patients with unexplained primary adrenocortical insufficiency.