Hypoadrenocorticism secondary to bilateral lymphomatous invasion of adrenocortical tissue was diagnosed in 2 adult castrated domestic shorthair cats. In both cats, findings during initial physical examination (ie, lethargy, anorexia, weight loss, and severe weakness) were consistent with severe hypoadrenocorticism. Hyperkalemia, hyponatremia, and azotemia were also detected, which were consistent with hypoadrenocorticism. Hypoadrenocorticism was documented on the basis of finding low baseline and ACTH-stimulated serum cortisol concentrations. The cats initially responded well to treatment, but both owners chose to have the cat euthanatized. Multicentric lymphoma with infiltration and destruction of the adrenal glands was confirmed during necropsy.