Scabies is one of the important neglected tropical skin diseases which caused by the parasitic mite Sarcoptes scabiei. Scabies is usually detected in the developing countries. This study was designed to investigate the molecular characterization and pathological alterations induced by mite infestation in sheep at Ismailia province, Egypt. A total of 760 sheep aged from 3 months to 3 years were examined during the period from October 2017 to March 2019. Among them, 80 (10.5%) were infested with one species of mites Sarcoptes scabiei. Molecularly, the second internal transcribed spacer (ITS-2) of nuclear ribosomal DNA (rDNA) was as a genetic marker. TheITS-2 primer was amplified from individual mites by polymerase chain reaction (PCR) revealing the diagnostic specific band at 480 bp, nucleotides sequencing proved the species.  Grossly, alopecia with rough leathery and corrugation of skin, erythema, crusts and pruritus were observed. The associated histological lesions were hyperkeratosis with crusting and thickening of the epidermis, acanthosis and vesiculation.