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RASSF1A is one of the most frequently inactivated tumor suppressors yet identified in human cancer. It is pro-apoptotic and appears to function as a scaffolding protein that interacts with a variety of other tumor suppressors to modulate their function. It can also directly bind the K-Ras oncoprotein and may serve to integrate pro-growth and pro-death signaling pathways. A SNP has been identified that is present in approximately 20% of Caucasians. Several studies have now presented evidence that this SNP is associated with an enhanced risk of developing cancer. Here we discuss the potential role of this SNP in cancer development and describe potential differences in function between the wild type and SNP containing protein.