We have demonstrated the intracellular expression of sex hormone-binding globulin (SHBG) exon VII splicing variant mRNA in human uterine endometrial cancer using the reverse transcription-PCR-Southern blot and DNA sequencing analyses. Analysis of the missing base pairs proved that they corresponded to the entire exon VII, which is considered to encode a portion of the steroid-binding site, suggesting that the steroid-binding affinity of this variant might be different from that of the SHBG wild type. In uterine endometrial cancers, the wild-type mRNA levels significantly (P < 0.01) decreased, and the ratio of the SHBG variant to wild-type mRNA levels (P < 0.01) increased with the advance of histological dedifferentiation. These results suggest that dedifferentiation of endometrial cancers might induce a reduction in their estrogen-dependent properties via intracellular SHBG.