Key clinical signs as well as gross and microscopic features that are most useful for differentiating Mareks disease from lymphoid leukosis and reticuloendotheliosis include:

Age: Mareks disease can affect birds at any age, including <16 weeks of age;
Clinical signs: Frequent wing and leg paralysis;
Incidence: >5% in unvaccinated flocks;
Potential nerve enlargement;
Interfollicular tumors in the bursa of Fabricius;
CNS involvement;
Lymphoid proliferation in skin and feather follicles;
Pleomorphic lymphoid cells in nerves and tumors; and
T-cell lymphomas.In addition to gross pathology and histology, other advanced procedures used for a definitive diagnosis of Mareks disease include immunohistochemistry to identify cell type and virus-specific antigens, standard and quantitative PCR for identification of the virus, virus isolation to confirm infections, and serology to confirm/exclude infections. The World Organisation for Animal Health (OIE) reference laboratory for Mareks disease is Avian Viral Oncogenesis group (led by Professor Venugopal Nair OBE) at The Pirbright Institute, UK.PCR blood testing can also detect Mareks disease, and proper testing can differentiate between a vaccinated bird with antibodies and a true positive for Mareks disease. Mareks disease is not treatable, however, supportive care can help. It is recommended that all flocks positive for Mareks disease remain closed, with no bird being introduced or leaving the flock. Strict biosecurity and proper cleaning is essential, using products like Activated Oxine or Virkon S and reducing dander buildup in the environment. Proper diet, regular deworming and vitamin supplements can also help keep infected flocks healthier. Reducing stress is also a key component, as stress will often bring about illness in birds infected with Mareks disease.
A step-wise process has been proposed for diagnosis of Mareks disease, which includes:

History, epidemiology, clinical observations and gross necropsy;
Characteristics of the tumor cell, and;
Virological characteristicsThe demonstration of peripheral nerve enlargement along with suggestive clinical signs in a bird that is around three to four months old (with or without visceral tumors) is highly suggestive of Mareks disease. Histological examination of nerves reveals infiltration of pleomorphic neoplastic and inflammatory lymphocytes. Peripheral neuropathy should also be considered as a principal rule-out in young chickens with paralysis and nerve enlargement without visceral tumors, especially in nerves with interneuronal edema and infiltration of plasma cells.The presence of nodules on the internal organs may also suggest Mareks disease, but further testing is required for confirmation. This is done through histological demonstration of lymphomatous infiltration into the affected tissue. A range of leukocytes can be involved, including lymphocytic cell lines such as large lymphocyte, lymphoblast, primitive reticular cells, and occasional plasma cells, as well as macrophage and plasma cells. The T cells are involved in the malignancy, showing neoplastic changes with evidence of mitosis. The lymphomatous infiltrates need to be differentiated from other conditions that affect poultry including lymphoid leukosis and reticuloendotheliosis, as well as an inflammatory event associated with hyperplastic changes of the affected tissue.