Paired fine-needle aspiration specimens were analyzed from 41 surgically resected thyroid nodules, to compare diagnostic accuracy, amount (absent, mild, moderate, or marked) and pattern (diffuse, droplets, or both) of colloid, nuclear detail (poor, satisfactory, or excellent) and cytoplasmic detail (intact or disrupted) in ThinPrep (TP) (Cytyc, Marlborough, MA) versus conventional smear (CS) cytologic preparations. The 41 surgical specimens included 25 colloid nodules, 6 papillary carcinomas, 4 follicular adenomas, 2 minimally invasive (encapsulated) follicular carcinomas, 3 Hashimoto's thyroiditis, and 1 Grave's disease. Both techniques identified seven of the eight carcinomas with the minimally invasive follicular carcinomas categorized as hypercellular follicular nodule, possibly malignant (HCFN). One papillary carcinoma was classified as a HCFN by both TP and CS techniques. The four follicular adenomas were classified as HCFN based on the TP slides. One oxyphilic follicular adenoma, associated with focal lymphocytic thyroiditis, was misinterpreted as Hashimoto's thyroiditis on a conventional smear. Three colloid nodules were interpreted as HCFN based on the TP slides. Two of these were similarly classified based on the conventional smear. ThinPrep slides contained less colloid and the colloid occurred as droplets rather than a diffuse pattern. TP slides had better nuclear detail but more often disrupted cytoplasm. In conclusion, the TP process does alter some cellular features; however, we experienced similar diagnostic accuracy with the TP and conventional smear preparations.