The expression of nm23 gene products has been associated with a lower metastatic potential and better outcome in malignant tumors. We have used immunohistochemistry to study the expression of nm23 protein in thyroid tissues from 101 patients consisting of 78 malignant neoplasms, 13 adenomas, and 10 other benign conditions. Cytoplasmic staining for nm23 protein was identified in normal tissues and in most benign and malignant lesions and did not correlate with either histological type of clinical outcome. Nuclear staining was seen in 93% of normal tissues and in 29% of primary carcinomas of the thyroid and was associated with a longer disease-free survival (P = 0.03). Membranous staining was present in some tumors but absent in normal thyroid. In conclusion, nm23 protein has a combined pattern of distribution among subcellular compartments in thyroid tissues. Although there was no significant association between cytoplasmic or membranous expression and histological type of tumor or survival nm23 nuclear expression may be a useful marker in assessing the evolution of thyroid tumors.