Aim-Background: Well-differentiated thyroid neoplasms with follicular architecture may often cause diagnostic difficulties, due to ambiguous pathological features. The aim of the present study was to investigate the immunohistochemical expression of a panel of markers, comprising cytokeratin-19, cytokeratin-20, galectine-3, ceruloplasmin, lactoferin, secretory component, HBME-1, calcitonin, chromogranin-A, TTF-1, synaptophysin and thyroglobulin, in well-differentiated thyroid neoplasms with a special emphasis on atypical neoplasms and to investigate their possible diagnostic role. Methods: A series of 148 cases of papillary carcinomas, 21 cases of follicular carcinomas, 50 cases of follicular adenomas and 21 cases of atypical neoplasms was collected from the registry or the files of the Department of Pathology of Areteion Hospital. Each case was examined for its immunohistochemical expression of markers. Results: Atypical neoplasms expressed Cytokeratin-19 in 15/21 cases, Cytokeratin-20 in 3/21 cases, galectine-3 in 12/21 cases, ceruloplasmin in 7/21 cases, secretory component in 8/21 cases, lactoferin in 4/21 cases, HBME-1 in 9/21 cases, TTF-1 in 3/21 cases and thyroglobulin in 4/21 cases. No reactivity was noted for calcitonin, chromogranin-A and synaptophysin in any of the cases we studied. Conclusions: The immunohistochemical reactivity of atypical neoplasms seems to be located between those of either papillary carcinomas and follicular adenomas or follicular carcinomas and follicular adenomas, which supports the theory of their possible common histogenetic link. The above mentioned panel of markers seems to contribute only slightly, if at all, in the differential diagnosis of those lesions.