**Abstract**

This chapter deals extensively with the role of Fibulin-3 (Fb-3) as early marker of malignant development, triggered by direct and long exposure to asbestos or asbestiform fibers. Asbestos has widely been used in many civic and industrial environments. Despite numerous countries, e.g., the European Union and the United States, have forbidden its production as well as utilization, still nowadays millions of tons of asbestos are manufactured worldwide. When inhaled, it causes the onset of malignant mesothelioma (MM) and several other types of cancer, including lung cancer. Health surveillance of subjects formerly exposed to asbestos is based on an early detection of major asbestos-related pathologies. However, the protocols adopted so far do not meet the sensitivity and specificity requirements needed to ensure an early diagnosis. Among the various eligible MM biomarkers, scientists have recently proposed Fb-3, which is a glycoprotein belonging to extracellular matrix proteins, coded through EFEMP-1 gene 2p 16 chromosome). Fb-3 is expressed by mesenchymal cells and plays a role in angiogenic processes as well-regulating cell-to-cell and cell-to-extra cellular matrix communication. However, it is weakly expressed also in healthy tissues. Previous studies conducted on MM historically asbestos-exposed patients have shown, on several biological matrixes such as serum and plasma, high Fb-3 concentrations. In the same way, high levels of circulating Fb-3 were observed in subjects exposed to a natural asbestiform fiber called fluoro-edenite (FE). Direct association between an increased Fb-3 expression and exposure to FE fibers has also been found in *in-vitro* and *ex-vivo* studies.

**Keywords:** fibulin-3, mesothelioma, asbestos, asbestos like fibers, biomarker
