The current work was carried out to reveal the probable cause that increases the seriousness of lumpy skin disease (LSD) in crossbred dairy cattle in villages of Assiut and Sohag Governorates, Upper Egypt. The serious form of LSD infected twenty-eight crossbred dairy cows. Diagnosis is based on the clinical background and histopathology. All cows were adult and previously vaccinated against LSD using the sheep pox “Romanian-strain” vaccine. Clinically, enormous numbers of hideous necrotic dermal lesions, similar to starred-shaped craters, were the prominent signs of the diseased cases in association with systemic reactions anorexia pyrexia, tachycardia, tachypnea, and edematous lymphadenitis in superficial nodes. Detailed clinical findings are described. Histopathologically, fibrinoid vasculitis, with severe perivascular mononuclear inflammatory cellular infiltration and ambulance of eosinophilic intracytoplasmic inclusions in the dermis were conspicuously histopathological findings. Blood films and lymph smears of the diseased cases revealed both erythrocytic and lymphocytic forms of Theileria infection. Theileria annulata was identified by polymerase chain reaction (PCR). Theileria annulata infection and LSD interactions were discussed. This tick-borne-protozoan is an endemic infection in our villages and plays a pivotal role in the frustration of the humoral and cell-mediated immune statuses of the infected cattle inducing reduction of the efciency of the applied vaccine, and increasing the seriousness of the endemic lumpy skin disease. A national strategy for reducing or minimizing the infection rate with Theileria infection should be warranted in paralleling vaccination programs to avoid the insufficiency of immune responses. The current work concludes that bovine theileriosis is an endemic disease in our villages and the existence of Theileria annulata infection minimizes the efficiency of the vaccination programs and increases the seriousness of LSD in crossbred cattle. The existence of sporadic cases of cattle infected by LSD precipitates the disease as a circulating disease in our villages in Egypt.