p53 gene mutations are the most frequent alterations in human cancers. In the published literature, a highly significant statistical difference between the prevalence of p53 mutations in haematological (H) and non-haematological (NH) malignancies can be found. However, no consistent reasons have been suggested to explain it. We propose two non-exclusive possibilities: (i) in H tumours p53 is altered with the same frequency as in NH tumours, but mechanisms other than mutations are involved and (ii) in H malignancies the prevalence of p53 mutations is much lower than in NH cancers because other genetic disturbances are involved. We hypothesized that retention of wild-type p53 in H cancers may be a consequence of: (a) the presence of telomerase activity in haematological cells and/or (b) the absence of hypoxia in the majority of H tumours.