Background: Lymphadenopathy is a common clinical finding with a broad spectrum of etiologies ranging from infections to malignancies. Histopathological examination of lymph node biopsies is crucial for a definitive diagnosis and effective management.

Aim: To analyze the clinicopathological spectrum of non-neoplastic and neoplastic lymph node lesions and correlate them with clinical parameters in the Indian population.

Materials and Methods: A prospective observational study was conducted over one year at Mahavir Institute of Medical Sciences, Vikarabad, involving 100 lymph node biopsy specimens. Clinical data were recorded, and histopathological examination was performed using H&E staining, along with special stains when necessary. Lesions were classified into non-neoplastic and neoplastic categories, and clinicopathological correlation was established.

Results: Out of 100 cases, 65% were non-neoplastic and 35% were neoplastic. Tubercular lymphadenitis was the most common non-neoplastic lesion (46.15%), while non-Hodgkin lymphoma (42.86%) was the predominant neoplastic lesion. The cervical lymph nodes were most frequently involved (60%), and the 21–30 years age group was the most affected. Males were more commonly affected than females.

Conclusion: Histopathological examination remains the gold standard for diagnosing lymph node lesions. Accurate clinicopathological correlation is essential for timely diagnosis, especially in regions with high prevalence of tuberculosis and increasing cancer burden.