The diagnosis is confirmed by bone marrow smears that show "giant inclusion bodies" in the cells that develop into white blood cells (leukocyte precursor cells). CHS can be diagnosed prenatally by examining a sample of hair from a fetal scalp biopsy or testing leukocytes from a fetal blood sample.

Under light microscopy the hairs present evenly distributed, regular melanin granules, larger than those found in normal hairs. Under polarized light microscopy these hairs exhibit a bright and polychromatic refringence pattern.

There are several manifestations of Chédiak–Higashi syndrome as mentioned above; however, neutropenia seems to be the most common. The syndrome is associated with oculocutaneous albinism. Persons are prone for infections, especially with "Staphylococcus aureus", as well as "Streptococci".

It is associated with periodontal disease of the deciduous dentition. Associated features include abnormalities in melanocytes (albinism), nerve defects, bleeding disorders.