A diagnosis of Gaucher disease is usually based upon histological or cytological examination of bone marrow specimens, a liver biopsy, or a surgically removed spleen. The presence of lipid-laden macrophages with striated cytoplasmic inclusions, the Gaucher-cells, is not specific for the disease. Many other diseases, including chronic myeloproliferative diseases, malignancies, and chronic inflammatory disorders, have been described as giving rise to so-called ‘pseudo-Gaucher’ cells. For a reliable diagnosis of Gaucher disease, histological examinations are neither necessary nor sufficient. The detection of low glucocerebrosidase levels in leukocytes or urine is pathognomonic of Gaucher disease and should therefore be applied in cases of suspected Gaucher disease. However, since the disorder is rare and its clinical manifestations may mimic lymphoma or other haematological diseases, a bone marrow or liver biopsy will usually be performed before a diagnosis of Gaucher disease is even considered, especially in the absence of known affected family members. For the detection of carrier status, enzyme assays have limited value because of the considerable overlap with normal subjects. In these cases, mutation analysis is warranted.