Malignant pleural mesothelioma is a highly aggressive tumor associated with 
asbestos exposure. There are few effective treatment options for mesothelioma, 
and patients have a very poor prognosis with a median survival of < 12 months 
from diagnosis. Biomarkers have been proposed as a cost-effective means of 
cancer management, and the search for a mesothelioma biomarker has been ongoing 
for the last 30 years. Many traditional soluble (glyco)protein biomarkers have 
been evaluated over this time, and an ever-increasing list of new biomarkers, 
including messenger RNA, DNA, microRNA, and antibodies, is being reported from 
biomarker discovery projects. To date, soluble mesothelin is the only tumor 
biomarker to receive US Food and Drug Administration approval for clinical use 
in mesothelioma. Mesothelin is a glycoprotein normally expressed on the surface 
of mesothelial cells, and in the cancerous state it can be present in 
circulation. Mesothelin has a limited expression on normal, nonmalignant tissue 
and is thus an attractive therapeutic target for mesothelin-positive tumors. In 
this review we will focus on the discovery and clinical usages of mesothelin and 
provide an update on other mesothelioma biomarkers and show how such biomarker 
studies might impact on the management of this deadly tumor in the future.