To elucidate the nature and significance of calcium oxalate crystals in the pathologic thyroid, we used polarized light microscopy to review 357 thyroid lesions. Under polarized light, calcium oxalate crystals had brilliant birefringence, and they were invariably identified within the colloid of follicles. The highest prevalence of crystals (87.9%) was in nodular goiters; they were also found in 60.0% of follicular adenomas and 33.3% of follicular carcinomas. The prevalence of crystals in papillary carcinomas was very low (5.4%). Therefore, the overall prevalence was 69.4% in benign nodules and 7.6% in malignant nodules. A heavy deposit of crystals was seen only in benign nodules except for one case of follicular carcinoma. Graves' disease, focal thyroiditis, and subacute thyroiditis showed low prevalence: 25.0,46.9, and 40.0%, respectively. In cases of toxic nodules, the crystals were sparsely identified within nodules, but abundantly observed in surrounding inactive tissues. Immunohistochemistry for thyroid hormones confirmed that the crystals tended to appear in inactive follicles. On tissue x-ray film, the crystals appeared as microcalcifications. As a result of these findings, we suggest that examinations of crystals are likely to be useful in the differential diagnosis of thyroid diseases and in possible estimations of the functional state of lesions.