p16Ink4a is a protein involved in regulation of the cell cycle. Currently, p16Ink4a is considered a tumor suppressor protein because of its physiological role and downregulated expression in a large number of tumors. Intriguingly, overexpression of p16Ink4a has also been described in several tumors. This review attempts to elucidate when and why p16Ink4a overexpression occurs, and to suggest possible implications of p16Ink4a in the diagnosis, prognosis and treatment of cancer. [ABSTRACT FROM AUTHOR]