The readily available technique of screening for gene polymorphisms could be used to explain inter-individual variability in a classic occupational interstitial lung disease, such as coal workers' pneumoconiosis (CWP). The objective of this paper is to describe candidate genes selected from the wide pool of cytokines and growth factors, and to discuss the applications and pitfalls when using them as biomarkers for susceptibility to CWP. The selection of candidate genes is mainly based on observed phenotypic changes in bronchoalveolar lavage (BAL) fluid or BAL cells of patients with CWP, or on animal experiments that use quartz as the fibrogenic agent. This paper also reviews the studies that have been performed to validate tumour necrosis factor genotype and phenotype with respect to CWP. Finally, it is proposed that a multiple marker approach to susceptibility to CWP should be used. This involves the measurement of two cytokines (tumour necrosis factor and transforming growth factor-beta) to improve denomination of high- and low-risk groups.