Proliferative capacity is an important determinant of tumour biological behaviour. For research and diagnostic purposes, immunohistochemical techniques are usually applied in the assessment of tissue proliferative status. An interesting alternative for these studies is a detection of histone mRNA. As the synthesis of histones is tightly coupled with DNA replication during S-phase of the cell cycle, histone mRNA level is a specific marker of S-phase cells. Furthermore, a short-lived transcript guarantees accurate estimation of S-phase cell pool at the moment of tissue fixation. The progress in molecular biology techniques during the last decade made possible the use of in situ hybridization, especially its non-radioactive version, in routine laboratory services. This technique can be successfully applied to detection of histone mRNA in routinely processed tissues. Advantages and limitations of such approach in tumour proliferation studies are discussed.