Clusterin (CLU) is a sulfated glycoprotein implicated in many physiological and pathological processes, including tumorigenesis. Several studies have reported the overexpression of CLU in human neoplasm, examined by immunohistochemistry. However, there are no extensive data on its role in the thyroid. Here we investigate CLU expression in thyroid tumors, and the potential correlation between this expression and clinicopathological parameters. Immunohistochemistry with anti-CLU was performed on paraffin sections from 39 thyroid tumors. Only medullary thyroid carcinomas (MTCs) were positive (n = 5). To confirm these results, 130 further cases (including 4 C-cell hyperplasia), their matched lymph node metastases (46 cases), and lymph node recurrences (10 cases) were analyzed. All MTCs were subdivided according to World Health Organization classification. Cytoplasmic positivity was scored qualitatively (weak, moderate, strong) and quantitatively on a 5-tier scale from 0, 1+ (<10% of cells positive) to 5+ (>75%). Statistical analysis was performed. CLU was expressed in normal C cells, C-cell hyperplasia, all MTCs, their lymph node metastases, and recurrences. There was a strong association between CLU score and the cellular type (P < .004). CLU score was inversely correlated with the presence of lymph node metastases (P < .0001). There were no differences between primary and metastatic or recurrent tumors. CLU expression is related to the cellular type and inversely correlated with the presence of lymph node metastases, which could represent a new positive prognostic factor.