To determine its usefulness as a specific diagnostic marker for follicular carcinomas (FCs) vs other follicular-patterned thyroid lesions and possible application to fine-needle aspiration specimens, we immunohistochemically studied peroxisome proliferator-activated receptor gamma (PPAR gamma) expression in histologic sections (FC, 13 cases; follicular adenoma [FA], 11; follicular variant of papillary carcinoma [FVPC], 9) and surrounding thyroid tissue by using a PPAR gamma monoclonal antibody. Positivity (detected by nuclear staining) was scored as absent, weak, moderate, or strong. When only moderate or strong nuclear staining was considered positive, 9 FCs (69%), 3 FAs (27%), and 2 FVPCs (22%) demonstrated positive nuclear immunoreactivity. The sensitivity and specificity of immunohistochemical detection of PPAR gamma expression in FCs were 69% and 75%, respectively. In nonlesional surrounding tissue, moderate to strong positive staining was seen in focal areas of chronic lymphocytic thyroiditis in 6 of 33 cases (FC, 2; FA, 3; FVPC, 1); diffuse moderate staining was detected in surrounding tissue in the absence of lymphocytic thyroiditis in 4 cases (12%; FC, 3; FA, 1). Staining in the follicular-patterned lesions and surrounding nonlesional thyroid was specific with peptide blocking experiments. PPAR gamma expression is not a specific marker for FCs, and its detection in nonlesional thyroid tissue suggests limited usefulness as a diagnostic marker for follicular-patterned lesions in general.