The ploidy pattern and the percentage of S-phase cells were investigated by means of flow cytometry using fresh or frozen samples in a series of 143 tumors and tumor-like lesions of the thyroid in an attempt to find whether there is any relationship between the histological characteristics of the lesions and their DNA content. The percentages of aneuploidy cases per category were: nodular goiter, 18.5% (15/81); fetal adenoma (including cases with trabecular/solid growth pattern), 58.3% (14/24); follicular adenoma other than fetal adenoma, 0% (0/18); papillary carcinoma, 11.1% (1/9); and minimally invasive follicular carcinoma, 57.1% (4/7). Regardless of the histological category, aneuploid lesions had a significantly higher (P < 0.001) percentage of S-phase cells (7.3%) than diploid lesions (4.1%). All the six cases with a DNA content within the triploid range were fetal adenomas, but one was a follicular carcinoma displaying a fetal adenoma-like growth pattern. The other three follicular carcinomas with an aneuploid DNA pattern also displayed foci of fetal adenoma-like growth pattern. Image cytometry of the four aneuploid follicular carcinomas showed similar DNA indexes in the peripheral, invasive foci of the lesions and in the central fetal adenoma-like areas. These results demonstrate that aneuploidy in benign tumors is restricted to adenomas displaying a fetal or fetal/embryonal growth pattern and support the concept that chromosome instability is a major pathway of tumorigenesis in thyroid follicular neoplasms.