Initially people with Acanthocheilonemiasis may have no symptoms. Symptoms occur more frequently in people who visit the areas where this parasite is common (endemic), than in people who are native to that area. One common laboratory finding, in people who have recently returned from infected areas, is abnormally high levels of specialized white blood cells (eosinophilia). Generally there are no symptoms associated with the laboratory finding.

When symptoms appear they may include itchy skin (pruritis), abdominal pain, chest pain, muscle pains (myalgias), and/or areas of swelling under the skin (subcutaneous). Examination by a physician may reveal an abnormally enlarged liver and spleen (hepatosplenomegaly), and abnormally high levels of granular white blood cells (eosinophilia). The adult worm (nematode) may lodge in the tissues of the abdomen and chest causing inflammation and immune reactions. This may result in inflammation of the lining of the lungs (pleuritis) and/or the membranes that surround the heart (pericarditis).

The early or prelarval form (microfilariae) of Acanthocheilonema perstans can be isolated from the blood from patients with Acanthocheilonemiasis. Generally this disease is diagnosed by the examination under a microscope of a thick blood smear taken from the patient.