Papillary variant of medullary carcinoma of the thyroid (MCT) is an unusual histologic pattern with some diagnostic difficulties. A case of encapsulated papillary variant of MCT with extensive cystic appearance is reported. A euthyroid, 43-yr-old woman with bone pain was incidentally found to have a 4.0-cm solitary, cold nodule on her left thyroid lobe. Histopathologic examination revealed an encapsulated tumor composed of a large cystic cavity with small papillary projections. The papillae were lined by multiple layers of neoplastic cells with small and regular nuclei containing condensed chromatin and lacking the characteristic "ground glass" appearance of the papillary carcinoma of the thyroid gland. Immunohistochemical studies revealed specific cytoplasmic staining of the tumor cells for calcitonin, chromogranin A, neuron-specific enolase, carcinoembryogenic antigen, and cytokeratin. Specific staining for thyroglobulin was not observed in any neoplastic cell. Staining with Congo red disclosed amyloid deposits within the stroma. The case was diagnosed as papillary variant of MCT. Medullary thyroid carcinomas may show a papillary pattern with a totally cystic gross appearance. Thyroid carcinomas should be classified according to their major immunoreactivity pattern rather than their morphologic pattern. Immunohistochemical and/or histochemical studies should be performed in all thyroid tumors that show unusual histologic features.