This study was designed to determine the clinical implications of intracellular expression of sex hormone-binding globulin (SHBG) wild-type and exon 7 splicing variant mRNAs in secondary spreading lesions of gynecologic cancers using the reverse transcription-polymerase chain reaction-Southern blot and DNA sequencing analyses. Compared with primary cancers, a relative increase in SHBG variant mRNA to wild-type mRNA expression was observed (4/10 cases of uterine endometrial cancers, 5/10 cases of uterine cervical cancers, 6/10 cases of ovarian cancers) or the expression of SHBG wild-type and variant mRNAs could not be detected (5/10 cases of uterine endometrial cancers, 3/10 cases of uterine cervical cancers, 4/10 cases of ovarian cancers). On the other hand, alteration to a relative increase in SHBG wild-type mRNA expression in the metastatic lesions occurred in only 3 cases (1/10 cases of uterine endometrial cancers and 2/10 cases of uterine cervical cancers) analyzed. These results suggest that the transcription of SHBG mRNA and the regulation of its splicing might be altered with metastatic potential, and this status might be involved in a change in steroidal dependency of metastatic lesions.