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Background: Palmoplantar keratoderma (PPK) is a heterogeneous group of hereditary or acquired disorders characterised by excessive epidermal thickening of the palms and soles. Proper knowledge about the aetiology of the disease and clinico-demographic profile helps in planning management and predicting outcomes. Aims and Objective: To determine the prevalence of different dermatoses and describe their clinico-histological correlation in acquired palmoplantar keratoderma. Materials and Methods: An institution-based cross-sectional study conducted after obtaining Ethics-Committee permission and consent from participants. Patients of any age or gender presenting with acquired PPK were recruited. The calculated sample size was 67 by using the prevalence rate (p) of 22.2%, allowable error (L) of 10%, the confidence level of 95% (z = 1.96), and an infinite population size of 20,000. Patients were evaluated by taking demographic and clinical data in a pre-designed case record form, necessary laboratory investigations and histopathological examination that wereevaluated by three blinded experts. The pooled data were analysed with statistical software. Results: Among the 67 participants, Psoriasis was diagnosed clinically in 39 (58.2%) and histologically in 7 (10.4%), Lichen planus (LP) clinically in 16 (23.9%) and histologically in 9 (13.4%), Pityriasis rubra pilaris (PRP) in 8 (11.9%) patients clinically and 7 (10.4%) histologically and Hyperkeratotic eczema (HKE) in 4 (6%) clinically and 43 (64.2%) histopathologically. There was very poor inter-rater agreement (Kappa = 0.148, SE 0.0047, 95% CI 0.057 to 0.24). The clinico-pathological correlation was found to be agreeable in 17.9% Psoriasis, 56.2% LP and 87.5% PRP. HKE was commonly misdiagnosed as Psoriasis in 65.1% of patients. Conclusion: Hyperkeratotic lesions of the palm and sole often present with overlapping clinical features and a skin biopsy has to be done to aid in diagnosis. Limitation: Stratification of the clinical expertise of clinicians was done during the analysis. [ABSTRACT FROM AUTHOR]