Though thyroid nodule is a common presentation, malignancy is rare. The present study was aimed at looking for biochemical predictors of malignancy in enlarged thyroid. This is a prospective study of all willing patients of the age group 18 to 70 years presenting with a complaint of thyroid swelling and underwent definitive surgery over a period of nineteen moths. All the subjects were initially evaluated with detailed history, physical examination, ultrasonography of neck and fine needle aspiration cytology (FNAC). A preoperative estimation of serum thyroid stimulating hormone (TSH), thyroglobulin (Tg) and anti-thyroglobulin (anti Tg) antibody were obtained. The plan of treatment was based on FNAC results and included hemi or total thyroidectomy. Based on permanent paraffin section report analysis was done. s: During the study period 110 patients underwent thyroidectomy, of which 92 patients met the selection criteria, of which 47 patients had malignancy on final histopathology. Majority were females, belonged to age group 30 to 60 years. The median serum Tg, TSH and anti Tg levels in benign group were 29ng/ml, 1.6mIU/L and 1.1IU/ml respectively where as in malignant nodules the same were 162ng/ml. 1.7mIU/L and 0.9IU/ml. On Receiver operating characteristic curve analysis, a Tg cut off value of 53ng/ml predicted malignancy risk with a sensitivity and specificity of 72% and 73% respectively (p<0.001). Our study showed usefulness of preoperative Tg values in predicting risk of malignancy. Its role should be further explored particularly in the backdrop of indeterminate cytology through a larger study.