The p16INK4A/CDKN2/MTS1 gene encodes a specific inhibitor of cyclin-dependent kinases (CDKs) 4 and 6. This study investigates p16INK4A gene status and expression in mesenchymal tumours, in particular soft tissue sarcomas (STSs). Employing non-radioactive polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) sequencing, no p16INK4A mutation was found in 86 samples taken from 74 mesodermal tumours with known p53 gene status. This suggests that p16INK4A gene alterations, inc contrast to p53, are not involved in the progression of STS. This finding is supported by the reports of a low frequency of deletions and intragenic mutations in STS. Furthermore, by immunohistochemistry (IHC), an inverse correlation was established between p16INK4A and RB positivity for 62 per cent of the frozen tumour samples investigated. However, alterations in other components of the pRh/p16INK4A/ CDK4/cyclin D1/E2F pathway have been proven crucial for tumourigenesis in human sarcomas.