Abstract: Objective:To evaluate the expression of Semaphorin 4C (Sema 4C) in breast cancer, endometrial cancer and prostate cancer tissues and seven cancer cell lines, including three human breast cancer cell lines (MDA-MB-435 S, MDA-MB-231 and MCF-7), two human prostate cancer cell lines (PC-3M-1E8 and PC- 3M-2B4), and two human endometrial cancer cell lines (AN 3CA and HEC- 1-B) and to determine its clinical significance.Methods: Highly sensitive SP immunohistochemistry was used to detect the expression of Sema 4C in 45samples of invasive ductal breast cancer, 42samples of endometrial cancer, and 49 samples of prostate cancer. Western blot was used to detect the expression of Sema 4C in the seven cancer cell lines. The subcellular localization of Sema4C was observed by cell immunofluorescence chemistry. Results: In human breast and en -dometrial cancer tissues, a high expression of Sema 4C was observed in cases with lymph node metastasis, with a significant difference ( P<0.05). In prostate cancer tissues, a high expression of Sema 4C was observed in cases with Gleason8-10(P<0.05). Western blot revealed that the expression of Sema4C was higher in high-metastatic cell lines (MDA-MB- 435 S, MDA-MB-231 , PC- 3M-1E8 and AN3CA cells) than in low-metastatic cell lines (MCF- 7, PC-3M-2B4 and HEC-1-B cells). The Sema 4C protein was mainly expressed in the cytoplasm and membrane. Conclusion:The expression of Sema 4C is universal in breast cancer, endometrial cancer and prostate cancer tissues and cell lines. Sema 4C may play a role in the metastasis of the three cancers.