Background:We focused on determining the most reliable transthoracic ultrasound (TUS) criteria that can predict malignancy of the pleural and peripheral pulmonary lesions and correlating our data with CT and cyto-histological findings. Sixty-nine patients (38 males and 31 females) were enrolled in our prospective study. They were divided into group I (48 patients), which included patients with pleural effusion, and group II (21 patients), which included patients with peripheral pulmonary lesions. All patients underwent chest X-ray (postero-anterior and lateral views), transthoracic ultrasound (TUS), CT chest, guided Tru-cut or surgical biopsies and histopathology, and/or needle aspiration and cytology. Results: In group I, the presence of pleural nodularity was a predictor of malignancy with significant statistical difference (b value < 0.001) and receiver operating curve (ROC) curve analysis showed pleural thickening cutoff value of 7 mm at a maximum combined sensitivity and specificity of 75% and 80% respectively and area under the curve 0.825. In group II, distorted intralesional vascular pattern, pleural, and chest wall invasion were statistically significant ultrasonographic malignant predictors (b values are <0.001, 0.016, and 0.004 respectively).Conclusion: TUS is a valuable and safe complementary method in differentiation between benign and malignant pleural effusion and peripheral pulmonary lesions but is not a substitute for CT.