Aim and objective: To determine the sensitivity, the specificity, the positive predictive value (PPV), and the negative predictive value (NPV) of ultrasound and cytology to detect malignancy for solitary thyroid nodules. Materials and methods: Prospective observational study conducted at a tertiary care hospital in India. The patients with solitary thyroid nodule, aged more than 12 years with consent of the patients/their parents and planned to undergo surgery, were included in the study. The patients were evaluated with history, examination, sonography, and cytology. Then, they planned for surgical hemi-/total thyroidectomy depending on indications, and the thyroidectomy specimens were sent to Department of Pathology for routine processing. Results: A total of 140 patients were considered for recruitment, but 80 patients were operated, and their data were analyzed. Sonographic findings were reported using thyroid imaging reporting and data system (TIRADS) classification, and the sensitivity was 75.00% with a specificity of 84.62% and PPV, NPV, and diagnostic accuracy of 72.41, 81.25, and 81.25%, respectively. Cytology was assessed by the Bethesda system for reporting thyroid cytopathology (TBSRTC), and considering Bethesda IV, V, and VI as true positives and Bethesda II as benign, the sensitivity and the specificity were 89.5 and 78.4%, respectively. When a composite analysis was performed, the sensitivity and the specificity of TBSRTC and TIRADS combined were 100 and 36%, respectively. The PPV and NPV were 45 and 100%, respectively, with the accuracy of 58.5%. Conclusion: The American College of Radiology TIRADS is a sensitive method to detect malignancy in thyroid nodules in Indian population with good specificity and PPV. Fine needle aspiration cytology (FNAC) was observed to be a sensitive technique having achieved a high sensitivity and NPV with a low specificity and PPV. The composite test (incorporating TIRADS and TBSTRC) had 100% predictive value for benign and malignant pathology.