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 ؋ 10 6 /L; range, 0-2460 ؋ 10 6 /L). Receiver operating characteristic curve analysis showed that 15 ؋ 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 ؋ 10 6 /L) to intermediate-risk (median, 112.8 ؋ 10 6 /L) and high-risk patients (median 666.1 ؋ 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 ؋ 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. (Blood. 2001;98:3249-3255)