The absolute content of CD34(+) cells in the peripheral blood of 84 patients with myelofibrosis with myeloid metaplasia (MMM) and 23 patients with other Philadelphia-negative (Ph(-)) chronic myeloproliferative disorders (CMDs) was investigated. In MMM, the median absolute number of circulating CD34(+) cells was consistently high (91.6 x 10(6)/L; range, 0-2460 x 10(6)/L). Receiver operating characteristic curve analysis showed that 15 x 10(6)/L as a decision criterion for CD34(+) cells produced an almost complete discrimination between MMM patients out of therapy and other Ph(-) CMDs (positive predictive value, 98.4%; negative predictive value, 85.0%). MMM patients with higher numbers of CD34(+) cells had a significantly longer disease duration (P =.019) and higher spleen volume index (P =.014), liver volume (P =.000), percentage of circulating immature myeloid cells (P =.020), and percentage of myeloid blasts (P =.000). When CD34(+) cells were correlated with the use of Dupriez risk stratification, CD34(+) cells increased significantly from low-risk (median, 68.1 x 10(6)/L) to intermediate-risk (median, 112.8 x 10(6)/L) and high-risk patients (median 666.1 x 10(6)/L) (F = 4.95; P =.009). When CD34(+) cells were correlated with a severity score on the basis of both myeloproliferative and myelodepletive characteristics of the disease, only the myeloproliferation index was significantly associated with CD34(+) cell level (F = 5.7; P =.000). Overall survival and interval to blast transformation from the time of CD34(+) cell analysis were significantly shorter in patients with more than 300 x 10(6)/L CD34(+) cells (P =.005 and.0005, respectively). In conclusion, the absolute number of CD34(+) circulating cells allows MMM to be distinguished from other Ph(-) CMDs; it is strongly associated with the extent of myeloproliferation and predicts evolution toward blast transformation.