Background Psoriasis is a chronic inflammatory skin disorder with complex pathogenesis involving immune-mediated, genetic, and environmental factors. This study aimed to investigate the immunohistochemical expression of Tumor Necrosis Factor-alpha (TNF-alpha) and Prolactin Receptor (PRLR) in psoriatic skin lesions, and to correlate these expressions with clinical parameters and recurrence rates over a six- month follow-up period. Methods This prospective study was conducted from March 2021 to October 2022 at the Department of Pathology, Ramaiah Medical College and Hospitals. Biopsies from immunohistochemically confirmed cases of psoriasis were included, with patients above 18 years of age. Skin biopsy specimens were processed for immunohistochemistry, with antigen retrieval, blocking, and staining for TNF-alpha and PRLR. Semi-quantitative scoring of staining intensity and positive cell count was performed, and overall expression scores were calculated. Results TNF-alpha exhibited consistent and predominantly severe expression across all cases, correlating strongly with disease severity and recurrence rates. In contrast, PRLR expression was minimal, especially in recurrent cases, suggesting its limited role in disease progression and treatment response.