Accumulation of information from scientific advances in genetics and biotechnology has accelerated research investigating the inherent individual variation in disease susceptibility and severity. Gene polymorphisms, in particular single nucleotide polymorphisms, are being evaluated for their role in multi-factorial diseases such as cancer and inflammation. Most surgical diseases are multi-factorial and a better understanding and utilization of the information gained from such studies by clinicians/surgeons is likely to favorably influence patient outcome. In this article, we illustrate the types of genetic variation and the complexities involved in their study and discuss their potential in predicting both the occurrence and outcomes of solid cancers.