Opportunistic infections are well documented in states of steroid excess. To our knowledge, histoplasmosis has not been previously reported in Cushing's disease, and has rarely been reported in patients with exogenous glucocorticoid use. We report a novel presentation of Histoplasmosis as pulmonary nodules in a patient with Cushing's disease. A 45-year-old man with a pituitary macroadenoma and Cushing's disease was treated with transsphenoidal hypophysectomy and radiation therapy. He was receiving Ketoconazole and basal steroid replacement, when he presented with dyspnea. Chest radiograph showed nodular lesions and subsequent biopsy revealed Histoplasma capsulatum. Itraconazole was administered and the patient recovered. The case not only demonstrates the protean manifestations of Histoplasmosis in patients with glucocorticoid excess but it also emphasizes the importance of intensive control of the hypercortisolemia in achieving a favorable outcome.