Background and Objective: Mediastinal masses in children are a heterogenous group of asymptomatic potentially life-threatening congenital, infectious, or neoplastic lesions that present complex diagnostic and therapeutic dilemmas. Materials and Methods: The clinical and laboratory features of 65 patients who had open biopsies in Ali-Asghar hospital over 11 years were reviewed. Results: Seventy-two percent of cases were male and 28% were female. The age varied between 2.5 months and 19 years. Eighty-four percent of lesions were malignant and 16% were benign. Neurogenic tumors were the most common (36.9%). In order of frequency the following lesions were the most common neuroblastoma (mostly in posterior mediastinum), Hodgkin’s and non-Hodgkin’s lymphoma (mostly in middle mediastinum), and malignant small round cell tumor (mostly in chest wall). Most patients were presented by fever (21.5%), dyspnea (20%) and cough (12%), especially in Hodgkin’s and non-Hodgkin’s lymphoma. Lymphadenopathy (29.2%) and hepatosplenomegaly (13.8%) were the most frequent clinical signs. Laboratory examination revealed anemia (29%), leukocytosis (35%), and high sedimentation rate (21.5%). Conclusion: The clinical presentation and laboratory findings of mediastinal and chest wall masses are often non-specific and are variable, but according to their clinical data (i.e. age) and location, only few important diagnoses should be considered.