Reduced expression of E-cadherin has been associated with loss of differentiation and/or increased invasiveness and metastatic ability in several types of neoplasms. Rare studies on thyroid tumors have shown minimal or absent expression in undifferentiated carcinomas and a variable degree of immunoreactivity/mRNA expression in follicular and papillary carcinomas. We studied immunohistochemically 2 follicular adenomas, 8 follicular carcinomas, 18 papillary carcinomas and 3 poorly differentiated carcinomas to evaluate E-cadherin expression. In 7 papillary carcinomas, lymph node metastases were also studied. The E-cadherin gene was analysed in 27 tumors by PCR/SSCP followed, whenever appropriate, by DNA sequencing. LOH at the E-cadherin locus was assessed in 16 tumors. Reduced and heterogeneous expression of E-cadherin was found in primary and metastatic papillary carcinomas, whereas follicular carcinomas showed moderate to strong homogeneous immunoreactivity, and poorly differentiated carcinomas showed no or very faint immunoreactivity. The only case harbouring a (missense type) mutation of the E-cadherin gene was a papillary carcinoma exhibiting immunoreactivity in the primary tumor as well as in metastasis. LOH was found in a follicular adenoma and in a poorly differentiated carcinoma without evidence of mutation in the remaining allele. Our results show that irreversible alterations (allele loss or mutation) of the E-cadherin gene are infrequent in thyroid tumors. The reduced and heterogeneous expression of E-cadherin in thyroid carcinomas, particularly of the papillary histotype, appears to reflect transcriptional regulation or post-transcriptional modulation rather than structural abnormalities.