INTRODUCTION Follicular thyroid carcinoma (FTC) is the second most common type of thyroid cancer. Genetic studies have demonstrated that the loss of expression and function of Cdk inhibitor p27 leads to the development of multiple-organ hyperplasia and malignancy, including thyroid carcinoma. AIM OF WORK (1) To assess the prognostic value of the quantitative expression of p27 in correlation with clinicopathologic prognostic indicators in FTC. (2) To explore its predictive value in the assessment of response to radioactive I-131 therapy in metastatic FTC patients. MATERIALS AND METHODS This retrospective study was conducted on 43 histopathologically confirmed FTC patients referred to the nuclear medicine department, National Cancer Institute, Cairo University between July 2001 and December 2010, for radioactive I-131 therapy. Clinicopathologic parameters, details of radioactive I-131 therapy and its outcome, and a serial follow-up serum thyroglobulin levels and I-131 whole body scan were obtained from their medical records. Quantitative expression of p27 using immunostaining was analyzed using paraffin blocks of thyroidectomy specimens in all patients. RESULTS With respect to clinicopathologic characteristics, p27 expression was found to be significantly lower in patients with vascular invasion (P=0.024) and in patients with an advanced-stage disease (P=0.048). A significant difference was detected between the risk stratification and the quantitative expression of p27. A statistically significant difference was obtained with respect to immunohistochemical expression of p27 between the metastatic and nonmetastatic patients as well as age, growth characteristics, tumor size, vascular invasion, and extrathyroidal extension. Despite the observed trend in patients with a low p27 expression, to have a worse response to iodine therapy, and a poor overall survival, the point of statistical significance could not be reached. CONCLUSIONS In this preliminary study, p27 quantitative expression appeared to provide a complementary valuable predictor with other prognostic variables for risk stratification in FTC patients. Response to I-131 therapy in FTC in relation to p27 expression should be thoroughly investigated including large-scale studies and more homogenous risk groups.