Tie-2 is an endothelial cell-specific receptor tyrosine kinase involved in vascular maturation and remodeling. Although its expression is considered to be restricted to vascular endothelial cells and hematopoietic progenitors, our immunohistochemical and in situ hybridization studies showed that Tie-2 and its ligand, angiopoietin (Ang)-l were expressed not only in benign and malignant human thyroid tumor cells but also in hyperplastic regions of adenomatous goiter. To confirm the expression in these tissues further, we used a laser capture microdissection system to isolate epithelial tumor cells from tissue specimens selectively, and demonstrated the expression of Tie-2 and Ang-1 mRNAs in tumor cells by RT-PCR analysis. Furthermore, Tie-2 and Ang-1 mRNAs and proteins were also detected in rat thyroid cell lines, FRTL-5 and PCCL-3. Our results suggest that Ang-1/Tie-2 signaling may be involved in the proliferation of thyroid epithelial cells.