Lumpy skin disease (LSD) is an infectious disease in cattle caused by a virus of the family Poxviridae, also known as Neethling virus. The disease is characterized by large fever, enlarged superficial lymph nodes and multiple nodules (measuring 2–5 centimetres (1–2 in) in diameter) on the skin and mucous membranes (including those of the respiratory and gastrointestinal tracts). Infected cattle also may develop edematous swelling in their limbs and exhibit lameness. The virus has important economic implications since affected animals tend to have permanent damage to their skin, lowering the commercial value of their hide. Additionally, the disease often results in chronic debility, reduced milk production, poor growth, infertility, abortion, and sometimes death.

Onset of fever occurs almost one week after infection by the virus. This initial fever may exceed 41 °C (106 °F) and persist for one week. At this time, all of the superficial lymph nodes become enlarged. The nodules, in which the disease is characterized by, appear seven to nineteen days after virus inoculation. Coinciding with the appearance of the nodules, discharge from the eyes and nose becomes mucopurulent.

The nodular lesions involve the dermis and the epidermis, but may extend to the underlying subcutis or even to the muscle. These lesions, occurring all over the body (but particularly on the head, neck, udder, scrotum, vulva and perineum), may be either well-circumscribed or they may coalesce. Cutaneous lesions may be resolved rapidly or they may persist as hard lumps. The lesions can also become sequestrated, leaving deep ulcers filled with granulation tissue and often suppurating. At the initial onset of the nodules, they have a creamy grey to white color upon cut section, and may exude serum. After about two weeks, a cone-shaped central core of necrotic material may appear within the nodules. Additionally, the nodules on the mucous membranes of the eyes, nose, mouth, rectum, udder and genitalia quickly ulcerate, aiding in transmission of the virus.

In mild cases of LSD, the clinical symptoms and lesions are often confused with Bovine Herpesvirus 2 (BHV-2), which is, in turn, referred to as pseudo-lumpy skin disease. However, the lesions associated with BHV-2 infections are more superficial. BHV-2 also has a shorter course and is more mild than LSD. Electron microscopy can be used to differentiate between the two infections. BHV-2 is characterized by intranuclear inclusion bodies, as opposed to the intracytoplasmic inclusions characteristic of LSD. It is important to note that isolation of BHV-2 or its detection in negatively-stained biopsy specimens is only possible approximately one week after the development of skin lesions.