Background: Thyroid cancer is a very common malignancy of endocrine system with increasing incidence rate over the previous two decades. Most thyroid cancers are well-differentiated papillary carcinomas or follicular carcinomas. Several risk factors have been attributed to the development of thyroid carcinomas such as exposure to ionizing radiations, iodine uptake, and Hashimoto's thyroiditis. In addition to environmental factors, genetic factors are involved in thyroid cancer. RET/PTC translocation plays a role in pathogenesis of differentiated thyroid carcinoma. The most common rearrangement types are RET/PTC1 and RET/PTC3, which are found mainly in papillary thyroid carcinoma. Objective: To study the association between RET/PTC translocations and differentiated thyroid carcinoma, its clinical implications and the role RET/PTC translocations in tumor genesis and aggressiveness. Patients and Methods:This prospective study was conducted on 100 patients with provisional diagnosis of nodular goiter underwent thyroidectomy. Detection of RET/PTC1 translocation was studied in our patients within thyroid nodules. After full history taking, examination and investigation for 100 patients, who underwent thyroidectomy postoperative pathology and were 25 malignant 75 benign cases. Specimens from this 100 cases were subjected to RET/PTC1 translocation testing. Results:The incidence of RET/PTC1 gene translocation was 8 case of 25 cases of malignant cases (32%), and three cases of 75 benign cases (4%). Conclusion: RET/PTC1, RET/PTC3 translocation plays an important role in the pathogenesis of differentiated thyroid cancer. The RET/PTC1, RET/PTC3 translocations were significantly associated with differentiated thyroid cancer especially papillary variants.