The prevalence of thyroid nodules is increased in patients with Cushing's disease, but the possibility of an association between thyroid and adrenal nodules in other patient groups has not been formally tested. We have evaluated the co-existence of thyroid and adrenal nodules in retrospective and prospective autopsy studies. Retrospective (83 autopsies) and prospective (29 autopsies) blinded studies of thyroid and adrenal gland histopathology were performed by two experienced histopathologists in unselected autopsies. The presence of nodules, defined as areas of tissue having discrete edges within the gland parenchyma seen as a step difference between the cells or architecture adjacent to the nodule, was determined for each gland. No association was found between the presence of adrenal and thyroid nodules in either the retrospective or prospective studies (p>0.2 for both). In the retrospective study, 23% of specimens had thyroid nodules and 28% adrenal nodules. In the prospective study, 24% of specimens had thyroid nodules and 7% adrenal nodules. The proportion of patients with adrenal nodules in the prospective study was significantly less than that in the retrospective study. In conclusion, thyroid and adrenal nodules are frequent autopsy findings in the general population but we have found no evidence of a relationship between the occurrence of nodules in these glands.