OBJECTIVE: Lactoferrin is an iron-binding protein that has been used for distinguishing normal from neoplastic conditions in many different tissues. In order to improve evaluation of thyroid lesions, we studied the lactoferrin immunoreaction in cytologic smears obtained by fine needle aspiration and in biopsy samples from primary neoplasms and from adenomatous goiter. STUDY DESIGN: A retrospective study on Foe needle aspiration cytology samples and corresponding available biopsies from thyroid lesions in patients examined at Sao Paulo County Hospital between 1982 and 1992, performed in order to evaluate lactoferrin immunoreactivity in morphologically well characterized samples from neoplastic and nonneoplastic lesions. Immunoperoxidase procedures were performed using monospecific polyclonal rabbit antihuman lactoferrin as a primary antibody and biotinylated goat antirabbit IgG as a secondary antibody. Amplification was performed with the avidin-biotin-peroxidase complex, and the color sign of the positive reactions was developed using a diaminobenzidine solution. RESULTS: Lactoferrin was not detected ivr cytologic smears from goiters, whereas only oi-le biopsy rc,ns slightly positive (1/21, or 4.76%). One smear front adenoma showed low positive staining (1/19, or 5.26%), which was The observation that lactoferrin present in 4 of 13 biopsies (30.77%) from adenoma. Papillary carcinomas were positive in 19 of 33 smears (57.58%) and in 100% of biopsies, whereas 31.25% (5/16) of follicular carcinoma smears were positive for lactoferrin, detected in all the biopsy samples. CONCLUSION: Lactoferrin immunoreactivity tons strongly associated with neoplastic proliferation and may be used as a useful auxillary marker to distinguish malignant from benign thyroid lesions lit cytologic smears and biopsy samples.