Preferentially expressed antigen of melanoma (PRAME) is a tumor antigen expressed in various malignant tumors including solid tumors and hemopoietic neoplasias but no or weak expression in normal tissues. The aim of this study is to determine the frequency and the clinical importance of PRAME expression in chronic myeloid leukemia (CML)/chronic myeloproliferative disorders (CMPD) and chronic lymphocytic leukemia (CLL). PRAME mRNA was measured by real time RT-PCR in 88 cases with chronic leukemia (CL) and 42 controls. Seventy cases had CML/CMPD (56 had chronic phase (CP)-14 had accelerated/blastic phase disease (AP/BP) and 18 cases had CLL (11 had early stage (Rai 0-I-II) and 7 had late stage (Rai III-IV). Mann Whitney U, Wilcoxon and Kruskal Wallis tests were used for statistical analyses. Twenty-four of 70 (34%) cases with CML/CMPD and 5 of 18 (28%) cases with CLL showed PRAME expression. Totally 29 of 88 cases showed PRAME expression (33%). However, only two controls showed weak PRAME expression. The difference for PRAME mRNA between the CLs and controls was significant (p = 0.000). PRAME (+) and PRAME (-) cases were not different for age, Hb, Hct, WBC count, platelet count, stage of the disease and response to therapy. PRAME was monitorised in eight cases during follow-up: in three cases PRAME was negative at CP and expression developed at the AP/BP disease. PRAME was positive at the beginning in five cases (4 CML-1CLL) and expression disappeared after chemotherapy. In conclusion, PRAME is detected in one third of the cases with CLs. PRAME mRNA changes may be detected during the progression of these disorders and/or after therapy. PRAME mRNA may be a useful marker to detect the minimal residual disease (MRD) and to determine the response to therapy in CLs.