The current investigation studied an outbreak of lumpy skin disease of cattle in Beni-Suef and Al-Fayium governorates from March up to September 2006. Epidemiological data over a total of 5500 cattle from all ages, breeds and sexes were investigated. Prevalence of lumpy skin antibodies was screened by enzyme-linked immunosorbent assay (ELISA) that revealed high exposure rates; 57% and 51.42% in Beni-Suef and Al Fayium governorates respectively Virus isolation was conducted on chorioallantoic membrane (CAM) of specific pathogen free embryonated chicken egg (SPF-ECE) and MDBK cell culture. The virus identity was confirmed by passive haemagglutination and polymerase chain reaction (PCR) on the infected CAM and MDBK cell culture. Experimental infection of rabbits was successful, demonstrating their possible roles in the epidemiological process of the disease.