Although most papillary thyroid carcinomas behave as low-grade neoplasms and are generally associated with a good prognosis, some subgroups of these neoplasms represent more aggressive variants. In order to determine if differences in the behavior of these papillary carcinomas were related to expression of growth factors or cell-cycle proteins, we analyzed a series of papillary carcinomas including the conventional or usual type (n = 27), tall cell (n = 27), diffuse sclerosing (n = 5), and columnar cell (n = 2) variants for expression of transforming growth factor beta (TGF beta),TGF beta receptors (TGF beta-RI and II, the proliferation marker Ki-67, and for the cell-cycle inhibitory protein p27(Kip)1 (p27). All groups of thyroid tumors expressed TGF beta and TGF beta-RI and RII by immunohistochemical staining. There was a marked increase in the Ki-67 labeling index after staining with antibody MIB-1 in the columnar cell tumors compared to the other groups, but this difference was not significant because of the small number of tumors in this group. The cell-cycle inhibitory protein p27 was expressed in all groups and was not significantly different between groups. Normal thyroid cells had a higher labeling index for p27 compared to papillary carcinomas. These results indicate that TGF beta and TGF beta receptors I and II are commonly expressed in the usual and in variant forms of papillary thyroid carcinomas, and that there is decreased expression of p27 protein in all of these neoplasms compared to normal thyroid. The biological basis for the more aggressive behavior of these variants of papillary thyroid carcinoma remains uncertain.