Histologic, histochemical, immunocytochemical, and ultrastructural features of two cardiac myxomas containing glandular elements are reported. Glandular elements in both cases stained positively with both mucicarmine and periodic acid-!khiff reagent with diastase pretreatment (DPAS). Immunoperoxidase studies demonstrated positivity of the glandular cells for carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), and keratin. Factor VIII-related antigen (FVIIIAg) was identified only in cells lining vascular spaces. Electron microscopic study of one tumor demonstrated well-formed glands having basement membranes, junctional complexes, and apical secretory granules. These findings indicate the capacity for true epithelial differentiation of cardiac myxomas and have implications both as regards the histologic diagnosis of these tumors and their histogenesis. Cancer 59:1767-1775, 1987. ARDIAC MYXOMA is the most common primary tu-C mor of the heart,',* and is considered by most authors to be a mesenchymal neoplasm and not merely the result of a thrombotic proce~s.',~-~ One characteristic of myxomas which has been cited as evidence for their neo-plastic nature is the occasional presence of histologically distinct gland-like elements within tumors which are otherwise grossly and microscopically typical of m y ~ o m a. ~ Although previous studies of cardiac myxomas have described the light m i c r o s ~ o p i c ~ ~ ~ and ultra~tructural~ features of such glandular elements, studies of the immu-nohistochemical characteristics of these structures have been limited to the demonstration of positivity for Factor VIII-related antigen (FVIIIAg), a finding which has been interpreted as supporting an endothelial origin for these turn or^.^ Although other ultra~tructural~~~ and immuno-histochemical' studies of cardiac myxomas have demonstrated tumors comprising a heterogeneous population of cells with features of endothelium, smooth muscle cells,