The high frequency of RASSF1A methylation has been noted in a vast number of patients in a broad spectrum of malignancies, suggesting that RASSF1A inactivation is associated with cancer pathogenesis. However, whether this recurrent incidence of RASSF1A hypermethylation in human malignancies and its association with more aggressive tumour phenotype is a frequent event across different cancer types has not yet been discussed. In this review, we interrogated existing evidence for association of RASSF1A hypermethylation with clinicopathological characteristics that can indicate more invasive lesions.