The clinical and pathologic features in 18 cases of multilocular thymic cyst (MTC) of the anterior mediastinum unassociated with Hodgkin's disease or seminoma were studied. The majority of cases were asymptomatic and discovered incidentally on routine chest x-ray. Several patients presented with acute symptoms of chest pain or discomfort, sometimes associated with dyspnea. Two cases had an incidental thymoma, and two had an incidental thymic carcinoma. The main histologic features of MTC included the following: multiple cystic cavities partially lined by squamous, columnar, or cuboidal epithelium (some having features of Hassall's corpuscles); scattered nests and islands of non-neoplastic thymic tissue within the cyst walls, often continuous with the cyst lining; severe acute and chronic inflammation accompanied by fibrovascular proliferation, necrosis, hemorrhage, and cholesterol granutoma formation; and reactive lymphoid hyperplasia with prominent germinal centers. These features suggest that MTC most likely results from the cystic transformation of medullary duct epithelium-derived structures (including Hassall's corpuscles) induced by an acquired inflammatory process. The changes are similar to those sometimes seen in association with thymic Hodgkin's disease and thymic seminoma, which are also probably due to the inflammation that accompanies these tumors rather than to the tumors themselves. We believe that MTC is pathogenetically analogous to a variety of cystic conditions of the head and neck region, for which the common denominator seems to be the induction of cystic transformation in ductular epithelial formations of branchial pouch or related derivation by an acquired inflammatory process.