Fine needle biopsy is generally considered unreliable in the differential diagnosis of follicular lesions of the thyroid gland. To test this hypothesis, we correlated fine needle biopsy diagnoses with surgical diagnoses in 379 follicular lesions. From nuclear characteristics (especially size) and the architectural pattern of tissue fragments, the following observations were made. Differentiation of goiters (including hyperplastic ones) from neoplastic thyroid disease is quite accurate and no more than 1 to 2% of cancers should be missed. The specific cytologic diagnosis of follicular carcinoma is 75% accurate, and that of follicular variant of papillary carcinoma is over 95% accurate. Of histologically proved follicular carcinomas, almost three-quarters should be diagnosed as such or strongly suspected by fine needle biopsy. The remainder will be identified as cellular follicular adenomas, reaffirming the overlap of cytologic features of benign and malignant neoplastic disease. From cytologic and surgical pathologic data for each fine needle biopsy diagnosis of follicular lesion, a probability of cancer can be stated that is useful in management decisions.