Thesis (MScMed (Dept. of Biomedical Sciences. Anatomy and Histology) --University of Stellenbosch, 2007. / Thyroid nodules are a common clinical problem encountered by physicians, surgeons and radiologists who deal with the head and neck region. However, most follicular lesions of the thyroid are benign, so that the indications for surgery should be as accurate as possible. The morphological difficulty on fine-needle aspiration biopsy (FNAB) of reliably distinguishing preoperatively between benign and malignant lesions has led to a search for ancillary methods that can assist with the diagnosis. The aim of the first study was to develop a cytological scoring system to improve diagnostic accuracy of fine-needle aspiration biopsy of papillary carcinomas with special reference to the follicular variant of papillary carcinoma. The objective of the second study was the application of immunodiagnostic markers Galectin-3 and HBME-1 to histology tissue sections and their corresponding fine-needle aspiration cytology smears to assess their value in distinguishing benign from malignant thyroid lesions. In the first study 16 different cytological features such as background, architecture and cellular morphology were quantatively assessed and scored. Only 14 of the 16 variables were statistically significant. The statistical analysis demonstrated that a score ≥ 4 was indicative of a papillary carcinoma with a sensitivity of 96%. A score < 4 suggested a benign multinodular goiter with a specificity of 97%. In the second study Galectin-3 and HBME-1 were applied to histology tissue sections and their corresponding fine-needle aspiration cytology smears. Statistical analyses showed that the sensitivity of immunohistochemistry for diagnosing malignancy was better than the immunocytochemistry, but the specificity of immunocytochemistry was superior. Furthermore the diagnostic accuracy of immunohistochemistry (86%) and immunocytochemistry (88%) using co-expression of these two antibodies was excellent. In this study on immunocytochemistry, papillary carcinomas were clearly identified with a 100% co-expression in the classic and 71% in the follicular variant of papillary carcinoma. For the surgeon the identification of papillary carcinoma is critical, as this determines the extent of surgery. Similary, the confirmation of a non-neoplastic lesion may prevent surgery. In most cases follicular neoplasms, benign or malignant, will usually be excised for histopathology, prior to definite therapy. These studies show that the implementation of ancillary methods such as a scoring system and immunodiagnostic markers can improve the diagnostic accuracy of thyroid fine-needle aspiration biopsies in our laboratory. This may lead to better management of thyroid nodules. However, it is advisable that cytopathologists always take all the clinical features and image analyses into consideration before making a diagnosis.