The histologic diagnosis of the follicular variant of papillary thyroid carcinoma (FVPTC) may be troublesome, especially in its encapsulated form. We evaluated the expression of galectin-3 (gal-3) and Hector Battifora mesothelial cell (HBME-1) in 200 formalin-fixed thyroid tissues with diagnosis of classical variant of papillary thyroid carcinoma or FVPTC, encapsulated or with infiltrative growth, with or without lymph node metastasis. All cases of classical variant of papillary thyroid carcinoma were consistently positive for gal-3; similar results have been obtained by using HBME-1. Interestingly, the invasive type of FVPTC, with or without metastasis, was strongly positive for gal-3 (78.2% and 96%, respectively), whereas only 46.8% of encapsulated FVPTCs without metastasis showed immunostaining for this marker. In the latter group, the HBME-1 expression achieved a significantly higher percentage of positivity (87%). Surprisingly, gal-3 immunodetection showed negative results in 4 encapsulated FVPTCs, despite the strong immunoreactivity in corresponding metastasis. Our data suggest that gal-3 immunodetection alone is not able to support the diagnosis of encapsulated FVPTCs.