Thyroid lesion can be neoplastic and non neoplastic, whether benign or Malignant. There are some cases in which pathologists have difficulties to differentiated those lesions. Aim: To analyze the expression of HBME-1 and E-cadherin on nodular hyperplasia, papillary carcinomas and follicular carcinomas. Paraffin blocks of nodular hyperplasia, papillary carcinoma and follicular thyroid were collected from Departement of Pathology Dr Soetomo General Hospital from January 1st, 2012 to December 31th, 2014. Immunohistochemical staining for HBME-1 and E-cadherin were performed. The difference of expression HBME-1 and E-cadherin were analyzed by Mann Whitney test, and the correlation between HBME-1 and E-cadherin determined using Spearman test. There were significant difference of HBME-1 expression between Nodular hyperplasia and Thyroid carcinoma(p≤0,05). There were also significant difference of HBME-1 between papillary and follicular carcinoma thyroid(p≤0,05). There were no significant difference of E-cadherin expression between Nodular hyperplasia and Thyroid carcinoma(p≥0,05). Conclusion: HBME-1 can be used as a marker to distinguish benign and Malignant lesion of thyroid gland, and also to distinguish papillary carcinoma and follicullar carcinoma thyroid.