Red blood cell mass (RCM) elevation is the sine qua non for diagnosis of polycythemia vera (pvera). The Polycythemia Vera Study Group (PVSG) employed therapeutic phlebotomy to lower the HCT to <55% as initial therapy. In the current era of frequent blood testing, RCM is usually requested based only on a high HCT often <55%. Thus the natural history of pvera may be changing if it is being diagnosed at an earlier stage. We reviewed 101 consecutive patients referred in 2002–2003 for RCM testing to characterize RCM requests from a large community referral base. There were 61 men and 40 women with mean HCT<55% (Table 1). 20 had lung disease or were smokers, 3 presented with arterial or venous thrombosis, 7 had cancer, 2 had renal cysts. HCT of men was higher than HCT of women if RCM was normal, but HCT were equivalent between genders if RCM was elevated. HCT was higher in men (p=0.0010) and women (p<0.0001) if RCM was elevated versus normal. HCT elevation was similar in secondary polycythemia vs pvera in men (51.0±4.02 vs 54.3±6.23; p=0.3397) or women (50.5±4.80 vs 49.3±2.12; p=0.4762).Table 1HCT of patients referred for RCM measurementGenderWhole GroupNormal RCMHigh RCMnHCTnHCTnHCTMale6148.3 (47.8) ±4.894546.9 (47.2) ±4.01652.1 (51.3) ±5.16Female4045.0 (43.8)± 4.723243.3 (42.5) ±3.691050.0 (50.0) ±3.84p value0.0001<0.00010.4932HCT shown as Mean (Median) ±SDWe examined whether, despite a lower presenting HCT, those with normal RCM demonstrated PVSG criteria that justified referral to our Nuclear Medicine department. Only 7 of the 75 patients with normal RCM met at least 2 of the PVSG “B” criteria or had splenomegaly, thus might have been diagnosed with pvera had RCM been high (Table 2).Table 22 PVSG “B” criteria or splenomegaly and normal RCMGenderWBC ≥12KPLT ≥400KB12 ≥900≥ LAP 100SplenomegalyM14.4413640158“normal”M12.1585133653“normal”M9.4428113968“normal”M8.6132134315 cmM8.231249218617 cmF18.258271923“normal”F6.3226318“enlarged”F7.114681315.3 cmOverall, 10 of 40 women and 16 of 61 men had an elevated RCM: 4 women and 5 men with polycythemia vera; 6 women and 11 men with secondary polycythemia. One other man was diagnosed with polycythemia vera on the basis of a borderline elevated RCM (33.8 ml/kg), normal O2 Sat on room air, popliteal artery thrombosis, and 3 “B” criteria. Serum erythropoietin (EPO) was low at 2.6 mU/ml (ref range 4–16). He was receiving therapeutic phlebotomy for hereditary hemochromatosis when his RCM was measured. He was the only patient with pvera whose EPO was low (three others had normal EPO levels). The 11 patients with secondary polycythemia who had EPO measured had normal levels. In summary, the HCT was the primary criterion for RCM testing for 2/3 of these patients. Only 5 presented with HCT>55%; mean HCT was ~50% in patients with elevated RCM. The bottom quartile HCT of women with elevated RCM in our patient population was 48.7%. This is a sensitive “cut-off” for finding an elevated RCM (p<0.0001, Chi square with Yates correction). We conclude that patients are referred for RCM testing when a high HCT is found, but at HCT far below the original PVSG parameters. Therefore polycythemia vera is now diagnosed earlier and in mostly asymptomatic patients. A normal EPO level does not rule out a diagnosis of pvera. A HCT < 48.7% may not warrant the measurement of RBC mass.