In this study, we examined the P15(INK4B) gene promoter methylation in patients with myelodysplastic syndrome and acute leukemia and its possible relationship with parvovirus B19 and Epstein-Barr virus infections. P15(INK4B) methylation frequency was significantly higher in acute leukemia patients than in that of non-malignant patients (P < 0.05). When the patients with myelodysplastic syndrome were included, no significant difference was found between these groups regarding the methylation status. The possible correlation between P15(INK4B) promoter methylation and parvovirus B19 infection was observed in adult acute leukemia patients (P < 0.05). However, no similar relationship in EBV-infected patients was observed. To the best of our knowledge, this is the first report showing the possible association between P15(INK4B) promoter methylation and parvovirus B19 infection in acute leukemia.