When a patient presents with weight loss, malaise, joint pain, and several nerve lesions, the diagnosis is usually suspected immediately and soon confirmed. However, polyarteritis can present in so many diverse ways that the diagnosis is not uncommonly delayed. Blood tests will show a marked inflammatory response with raised ESR and C-reactive protein. There is mild anemia, sometimes a raised white cell count, and low albumin, but none of these findings are specific to poly-arteritis nodosa. Rheumatoid factor may be positive, complement levels reduced, and hepatitis B markers positive.

A biopsy of involved tissue showing the typical pattern of destruction of the vessel wall of a small artery is the usual confirmatory test. Skin, muscle, testes (if involved), or a sensory nerve, the sural nerve, may be biopsied. If none of the involved tissue is accessible, an angiogram is performed. This involves the injection of dye into the arteries supplying the gut, liver, and kidneys and taking X rays that show the arterial system very clearly. In poly-arteritis nodosa affected arteries have an irregular diameter and typically appear beaded. The classical small aneurysms (localized dilatations along the arteries) are seen less often these days because of earlier diagnosis and treatment. It is important to rule out the possibility of infection and consider the presence of an underlying malignancy in all patients.

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