Background: The mediastinum is known to be a space within the domain of the thorax housing the important organs, blood vessels, nerves, lymphatics along with the surrounding connective tissue, where the International Thymic Malignancy Interest Group (ITMIG) classification system based on cross sections derived by the CT into prevascular mediastinum, visceral mediastinum and paravertebral mediastinum. The diagnosis of mediastinal neoplasia and it is necessary treatment often becomes challenging owing to the complex anatomy. With the advancement in cross-sectional imaging using CT scan with or without contrasts, diffusion weighted and chemical shift MR imaging, FDG-PET scan, guided biopsies with microscopic examination aided by special stains, the diagnosis of such become unconstrained. Materials and methods: In our aim to focus on the clinico-pathology locus, diagnosis and treatment of mediastinal neoplasia, we perform a retrospective study in a tertiary care hospital spanning from January 2020 to December 2022, for a period of 3 years in the CTVS Department (IPGMER and SSKM) Hospital, with the number being 42 who had mediastinal masses and they were characterized using the age, gender, clinical stigmata, and were subjected to cross-sectional imaging of the thorax, guided biopsies, histopathological examination, targeted treatment using surgery or the standard therapeutic approach. Result: Statistical analysis was done using the software SPSS version 20/21, revealing 28 males and 14 females (M:F = 2:1) 28.57% patients for hydatid cyst, 26.19% patients of thymoma, 7% patients for thymic malignancy, 11.90% of patients for lymphoma, 14.28% for pleuropericardial cyst, 9.52% for dermoid, and 2.38% for teratomas. The follow-up period ranged from 1 to 5 years and the mean follow-up was 2.33 ± 1.28 (Mean ± SD). lesions were mostly found in the anterior compartment of the mediastinum (20%) with thymoma being the commonest followed by hydatid, pleuropericardial cysts, dermoid and the lymphoma. Conclusion: Since they are deemed to be slow growing and gradually would compress the great vessels, heart, spinal cord, vocal cords, stellate ganglion, brachial plexus, superior vena cava, or the diaphragm to explain the symptomology, we have generously discussed and documented the atypical lesions too which must be taken as the differential diagnosis namely atypical lesions namely retrosternal goiters invading the mediastinum, Langerhans cell histiocytosis, mesothelioma, squamous cell carcinoma, adenocarcinomatous lesion, pleomorphic sarcomas, melanomas, primary pleural liposarcoma, malignant epithelioid gastro intestinal stromal tumors, and even solitary fibrous tumors. To sum up, specific radiology with the needle diagnosis and targeted treatment would henceforth be a logical approach to aim a better patient care.