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Aim: This study aimed to confirm the clinically diagnosed cattle with lumpy skin disease (LSD) at Baghdad Province/Iraq from October 2018 to March 2019. Materials and Methods: Molecular polymerase chain reaction (PCR) and histopathology were applied for the detection of LSD among 71 infected cattle issued for slaughter. Results: Pre-slaughter clinical examination showed significant increases (p<0.05) in values of temperature (39.7±0.74°C), pulse (96.42±3.51), and respiratory (33.54±0.63) rates. Enlargement of lymph nodes (prescapular, supramammary, and prefemoral), lacrimation, mucopurulent nasal discharge, salivation, edema in limbs and head among severe infected cases, and marked fall in milk production was seen. An association of LSD to risk factors (age, gender, and areas) showed that there is significant elevation in prevalence of disease in >2-5 years (54.93%) rather than other age groups (>5 and <2 years) in females (73.24%) than males (26.76%); and in sub-rural (42.25%) and rural (39.44%) compared to urban (18.31%) areas. Postmortem examination appeared nodular lesions in upper parts of the digestive system (9.86%), rumen (2.82%), upper respiratory tracts (7.04%), and lung (4.23%). The PCR examination of P32 and thymidine kinase antigenic genes showed 90.14% and 60.56% positive samples, respectively. Histopathological analysis of nodular skin biopsies showed edema, hyperemia, acanthosis, severe hydropic degeneration, and hyperkeratosis in epidermis; whereas, mononuclear cell infiltration, inclusion bodies, and vasculitis seen in the dermis. Conclusion: PCR and histopathology assay could be a potential method to confirm the LSD infection concomitant with clinical examination. [ABSTRACT FROM AUTHOR]