To investigate the incidence of p16 gene methylation in hematological malignancies, and the relations between p16 gene methylation and the prognosis of hematological malignancies.Fifty-five patients were studied by restriction enzyme polymerase chain reaction (PCR) to detect p16 gene methylation.p16 gene methylation was detected in 6 of 55 patients (10.9%), who were 1 patient with M2a, 1 patient with M5a, 2 patients with chronic myelogenous leukemia (CML) in blast crisis, 1 patient with progressing multiple myeloma (MM), 1 with non-Hodgkin's lymphoma (NHL) accompanied by B-ALL, respectively. p16 gene methylation correlates with adverse prognostic features. The patients with p16 gene methylation had poor response to therapy, and died shortly after p16 gene methylation was detected.The methylation of p16 gene plays an important role in the pathogenesis and the development of some hematological malignancies. The patients with p16 gene methylation have poor prognosis. The detection of p16 gene is a useful tool for evaluating prognosis of hematological malignancies.