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It is generally known that even with permanent sections, the differential diagnosis between follicular adenoma and follicular carcinoma is often difficult to determine. It is not unusual to encounter patients diagnosed with benign follicular adenoma whose diagnoses have to be changed to malignancies because of recurrence or metastasis. As the monoclonal antibody HBME-1 produced by mesothelioma cells has been shown to have reactivity in thyroid carcinomas, we investigated the diagnostic usefulness of HBME-1 in follicular neoplasms. Immunohistochemical staining for HBME-1 was performed on 205 various thyroid tumors using the labeled streptavadin biotin peroxidase method. When hematoxylin-eosin (HE) staining was performed again for this study and all cases were examined in accordance with the WHO Histological Classifications 2nd Edition, 87.2% (54/62) of adenomatous goiter and 72.6% (45/62) of follicular adenoma were negative. On the other hand, 84.6% (33/39) of follicular carcinoma and 97.2% (35/36) of papillary carcinoma were positive. All anaplastic (2/2) and medullary (4/4) carcinoma were negative. Examination in follicular neoplasms had a sensitivity of 84.6%, specificity of 72.6%, positive predictive value of 66.0% and overall accuracy of 77.2%. Among the cases treated as follicular adenoma clinically, the diagnosis of 13 cases was changed to follicular carcinoma, and 6 cases to papillary carcinoma for this study. These cases showed strong HBME-1 positivity. Two of the follicular carcinoma cases experienced recurrence. We conclude that immunohistochemical staining with HBME-1 may be useful clinically to pick out cases with a high risk of recurrence in follicular carcinoma, and that benign adenoma cases need close follow-up.