Recent studies have disclosed the presence of a second estrogen receptor (ER; ER-beta) in addition to a classical ER-alpha. ER-beta mRNA expression has yet to be studied in pancreatic cancers. Thus, we studied the expression of ER-alpha and ER-beta mRNA in pancreatic cancers (n=29) by real-time quantitative reverse transcriptase-polymerase chain reaction, and compared the expression levels in pancreatic cancers with those in breast cancers (n=116) which are typical estrogen-dependent tumors. Breast cancers were divided into two groups, ER-positive and ER-negative, according to the ER status determined by enzyme immunoassay. ER-alpha mRNA levels were significantly (P<0.01) higher in ER-positive (679.4+/-74.7 fmol/microg RNA) than ER-negative (159.7+/-33.4) breast cancers, and pancreatic cancers showed significantly (P<0.01) lower ER-alpha mRNA levels (17.5+/-10.0) than ER-negative breast cancers. On the other hand, ER-beta mRNA levels were significantly (P<0.01) higher in ER-negative (14.1+/-1.6) than ER-positive breast cancers (7.9+/-1.0), and pancreatic cancers showed significantly (P<0.01) higher ER-beta mRNA levels (28.1+/-5.1) than ER-negative breast cancers. Accordingly, ER-alpha/ER-beta mRNA ratios were significantly (P<0.01) lower in pancreatic cancers (0.94+/-053) than in ER-positive (203.9+/-34.5) and ER-negative (21.9+/-5.2) breast cancers. ER-beta2 mRNA variant expression was significantly (P<0.05) higher in pancreatic cancers than in ER-positive and ER-negative breast cancers, and, on the contrary, ER-beta1 mRNA variant expression was significantly (P<0.01) lower in pancreatic cancers than in ER-positive and ER-negative breast cancers. These results suggest a possibility that ER-beta (ER-beta2) plays a more important role than ER-alpha in pancreatic cancers.