While the majority of pituitary tumours will remain benign, a proportion will show invasive behaviour and a still smaller proportion will become malignant. Recent studies at both the biochemical and molecular level are now defining the changes associated with pituitary tumour initiation and progression. In particular, the use of microsatellite analysis in determining regions of gene deletion has considerably advanced our understanding of pituitary tumourigenenesis. Bringing together the data of several groups now allows a tentative map to be drawn showing loss of heterozygosity at several chromosomal loci to be associated with the transition to the invasive and malignant phenotype, while changes associated with chromosome 9p and silencing, through methylation, of the tumour suppressor gene p16 appear to occur early in pituitary tumourigenesis. At the biochemical level, immunohistochemical studies have defined changes in key regulatory proteins along this multistep pathway. To determine whether these changes are truly predictive of tumour behaviour awaits carefully designed prospective studies. These future studies may well aid decision-making regarding management in a manner not possible using current histological assessment.