The aims of the study were to identify medullary thyroid cancer (MTC) in its earliest stages by screening patients with basal calcitonin measurements and to determine whether basal serum calcitonin measurements should be a part of the routine evaluation of a nodular goiter. Basal serum calcitonin levels were obtained from 75 patients (female:male 57:18, mean age 42.8 years, range with 18-76 years) with nonnodular thyroid disease as controls. Their mean basal calcitonin level was 7.8+/-0.4 pg/mL with a range of 5-27 pg/mL. Seven hundred seventy-three patients with nodular goiter were included in the study (female:male 586:187) with the mean age of 46.1 years (range 17-78). Four patients had elevated basal serum calcitonin levels ranging between 150-1000 pg/mL. These 4 patients underwent surgery. MTC was confirmed by histopathology in all 4. One patient's mother and brother were also diagnosed as MTC as a result of family screening. Basal serum calcitonin levels were higher than 150 pg/mL in these patients. Fine needle aspiration biopsy (FNAB) of 2 of 4 MTC patients were incorrectly diagnosed as papillary carcinoma; another had malignant cytology and the fourth had benign cytology. None were diagnosed as MTC on the basis of FNAB. In conclusion, calcitonin measurement is an effective method for the diagnosis of MTC. Measurement of basal calcitonin levels in patients with malignant or suspicious FNAB may be a cost-effective approach to screen for MTC. High basal serum calcitonin levels increase the chance of curative therapy by diagnosing MTC in the early stages. It is superior to FNAB for diagnosis of MTC.