The variability of quartz hazard is related to the characteristics of particulate toxicants. Although these have the same chemical composition, they exist in various forms and surface states, each one eliciting different biological responses. On the basis of data from the literature, surface chemical properties are associated to the subsequent stages reported by Donaldson and Borm (1998) in the mechanistic model proposed for quartz carcinogenicity. Surface radicals and iron-derived reactive oxygen species (ROS) are implicated in oxidative stress, considered to be the key event in the development of fibrosis and lung cancer. Other chemical functionalities related to cytotoxicity, however, modulate the overall pathogenicity by regulating transport and clearance. The chemical features deriving from the intrinsic characteristics of a silica dust--e.g. its origin--as well as those generated by external factors--e.g. contaminants, associated minerals--are discussed in relation to their possible role in the pathogenic mechanism.